To investigate the current status of fear of disease progression (FoP) in patients with neuromyelitis optica spectrum disorder (NMOSD) and analyze its influencing factors. Methods: A total of 120 patients with NMOSD from the neurology outpatient and inpatient departments of a tertiary hospital in Wuhan were selected as participants between June 2024 and March 2025. The enrolled patients were assessed using the General Information Questionnaire, Fear of Progression Questionnaire-Short Form (FoP-Q-SF), and Medical Coping Modes Questionnaire (MCMQ), followed by statistical analysis. Results: The mean Fear of Disease Progression (FoDP) score among NMOSD patients was 36.57 ± 7.72. Of the participants, 48(40% ) exhibited moderate fear, and 66(55% ) demonstrated severe fear. Key influencing factors included avoidant coping, yielding coping, and the presence of refractory hiccups, nausea, or vomiting symptoms (all P<0.05). Avoidant coping showed a positive correlation with FoDP (P<0.01), while yielding coping negatively correlated with FoDP (P<0.01). Conclusion: Patients with NMOSD experience a high level of fear regarding disease progression. Clinical interventions should prioritize guiding patients to reduce avoidant coping strategies while addressing the psychological needs revealed by their yielding coping responses. Additionally, proactive management of refractory hiccups, nausea, and vomiting is essential to alleviate patients’fears effectively.