Asphyxia appears when Alex Shepherd finds Margaret Holloway strapped to a chair in the Otherworld Overlook Penitentiary, which he quickly frees her from. He shows her the locket that Elle Holloway gave to him, which belonged to Nora. The memories of Nora manifest and summon Asphyxia soon after. He escorts her to safety when Asphyxia emerges from a fleshy hole in the wall, attacking Deputy Wheeler and pulling him in. Holloway then seals the door behind her, smiling evilly as Alex is trapped in the chamber with her daughter's monstrous incarnation.
Asphyxia resembles a mass of female bodies gruesomely fused together in a chain. She has a single pair of legs, but no feet, and uses dozens of arms and hands to walk with, similar to a centipede; she snakes across the ground and uses them for striking. She lacks eyes and her mouth is usually covered by the upper hands growing out of her shoulders.
Asphyxia attacks with her numerous limbs, but she primarily strikes with her four main arms, often in a series of three swings. She can also spin around and knock Alex down with her long tail section, or simply charge him head on, as well as open her mouth and let out a ghastly shriek which can send Alex tumbling backwards.
Her weakness is that she is somewhat easy to dodge (though quite damaging), and her "tail" section is a weak vital point on her body; striking it hard stuns Asphyxia long enough to get a hit on her head. Successfully dodging Asphyxia's grapple attempt will leave her tail exposed and vulnerable. Striking Asphyxia's tail will bring her to her knees, leaving her head open to melee attack.
After taking enough damage, Alex forcibly parts the hands covering her mouth forcing her to breathe, killing her. Unlike the other bosses of the game, Asphyxia only has one combat form.
Asphyxia's name and appearance are symbolic of how Nora Holloway died: suffocation. Her mother, Judge Holloway, strangled her in order to sacrifice her, to appease the Order's dark God and protect Shepherd's Glen. The numerous hands choking and groping Asphyxia's body symbolize how she was murdered.
Nora loved to read, particularly Alice's Adventures in Wonderland, her favorite book. Having multiple arms, Asphyxia's form appears similar to that of the Caterpillar in the book and her "scream" is similar to how the Caterpillar blows smoke from his hookah at Alice. Joshua notes that Nora likes the Caterpillar on his photograph of her.
Asphyxia's appearance is heavily sexualized, evidenced in both her physical appearance and her sway-like, seductive movement, yet she is still unrevealing (vaginal area and breasts are covered in the same manner as a girl would try to cover herself), perhaps symbolizing how she was nearly a woman full grown but denied it.
As depicted in the game, Asphyxia exhibits a tormented existence. It is noted that there is a green substance emitted from her tail when she performs a swiping attack. Usually anything green emitted from the body is a sign of serious infection or is a toxin. The green substance can be attributed to poison; poison can be linked to the wellness, or lack thereof, concerning the soul or the mind.
Asphyxia's lack of eyes may also symbolize how Nora Holloway died. Normally, if a person loses consciousness, the lungs automatically seek air and the breathing functions continue, which makes it nearly impossible for someone to suffocate themselves. This could mean that Nora died half-conscious, half-unconscious, which would give the hands around Asphyxia's mouth a dual meaning; not only was she unable to breathe, she was given no reprieve, even once she blacked out.
- Asphyxia is one of only two bosses of Silent Hill: Homecoming (the other being Amnion) that was not responsible for the death of a parent, being an incarnation of the parent's memories of their murdered child. However, only Alex's intervention saved Margaret Holloway from a gruesome death at the hands of Asphyxia.
- Like many of the creatures and characters in Homecoming, Asphyxia was designed by artist Kenzie LaMar. Some of the original design sketches reveal she had tentacle-like feelers coming out of her breasts.
- Defeating Asphyxia in the Xbox 360 version unlocks the Achievement "Catch Your Breath".
- The name "Asphyxia" is Greek for "without heartbeat", typically linked with deprived oxygen levels in the body. This can lead to hypoxia, which in turn causes cyanosis (discoloration and malformations in the skin).
- Asphyxia's corpse is absent after she is killed; a cutscene of Joshua Shepherd occurs immediately after Alex defeats the boss, and once the player regains control, the body is gone without a trace, unlike the two prior bosses. This was likely an oversight by developers.