Shiori Misaka is a chronically ill 16-year-old high school student, afflicted since birth by an unnamed terminal condition that causes physical weakness and recurring school absences. Despite maintaining a cheerful, polite facade, she emotionally distances herself from others to avoid imposing her health struggles. Her fragile state is reflected in her signature attire: a white jumper and brown checkered shawl.

Her core conflict stems from her fractured bond with older sister Kaori, who denies their relationship to escape grief over Shiori's prognosis. Before Shiori's decline, they shared deep closeness. Shiori yearns for mundane shared experiences with Kaori, like attending classes or eating lunch together.

Shiori once attempted suicide in a park with a box cutter, intending to slit her wrists. This was interrupted when Ayu Tsukimiya accidentally triggered snowfall onto her, leading to an encounter with Yuichi Aizawa. His intervention halted her suicide and ignited her desire to reconnect with them both.

As her health worsens, Shiori gains temporary permission to attend school for one week. Yuichi arranges a café birthday party where Kaori arrives, reconciling by acknowledging their sisterhood. Shiori collapses shortly after and is hospitalized. Her illness then enters unexpected remission, defying its terminal prognosis. During recovery, she confesses she suppressed her terror of death behind a mask of fortitude and never truly wished to die.

In the Kaginado crossover, Shiori appears among Key franchise characters. She retains her polite demeanor, signature shawl, and habit of eating ice cream in any weather. No new storylines or character development expand upon her established Kanon background.