Like the other students, Nagito is annoyed by Usami. When Usami gives the students Usami Straps in the beginning of the school trip, Nagito is at first silent and continues smiling despite seeming clearly annoyed by the silly objects.
Many of the students distrust Nagito after the first trial. However, Usami believes in his good side and tries to encourage him to be more self-confident, make friends, and do good things. Unfortunately, Nagito doesn't take her seriously and, just like the other students, he considers her an annoyance.
In the Final Dead Room, he is mostly annoyed by her and asks her not to get in his way, though he will also ask her what's wrong when she cries. Monomi is one of few who cares about Nagito and believes in his good side. She tries to tell him this, but he ignores her, likely not considering her a person since she is seemingly a slow-witted plush toy. After Monomi was in the Final Dead Room with Nagito, she remarks that she is afraid of Nagito since he tried to shoot himself when he had to play Russian Roulette as the last part of the Final Dead Room.
In Danganronpa V3: Killing Harmony's non-canon Ultimate Talent Development Plan, Nagito during his school years at Hope's Peak Academy always saw Usami as a stuffed animal and never saw her as his teacher. This made Usami very upset since he never really accepted her as the teacher.
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Nagimi isn't a popular friendship among the Danganronpa fandom as it's often overshadowed by Komahina, due to Nagito always seeing Usami as a stuffed animal, he never saw Usami as his teacher and the fact they're also rivals, even though Usami sees Nagito as his friend in her side. Nagito is also always annoyed by Usami being another thing that can decrease Nagimi's popularity.