Purpose <p>To identify symptom clusters in nasopharyngeal carcinoma (NPC) survivors and to examine the potential indirect pathways that link them to perceived cognitive function via anxiety and depression.</p> Methods <p>This cross-sectional study recruited 556 NPC survivors by convenience sampling between November, 2024, and May, 2025. Data were collected using the Anderson Symptom Inventory, Generalized Anxiety Disorder Scale, Patient Health Questionnaire, and Functional Assessment of Cancer Therapy, and symptom clusters were identified using exploratory factor analysis. Symptom relationships with anxiety, depression, and perceived cognitive function were analyzed through structural equation modeling.</p> Results <p>Two distinct symptom clusters were recognized, a therapy side-effect cluster and a psychoneurological-physical cluster that exerted a direct negative association with perceived cognitive function through both a direct pathway (<i>β</i> = −0.126, 95% CI [−0.149, −0.096]) and three indirect mediating pathways: the independent indirect effects of anxiety (<i>β</i> = −0.064, 95% CI [−0.086, −0.048]), depression (<i>β</i> = −0.094, 95% CI [−0.110, −0.083]), and the sequential pathway of anxiety-depression (<i>β</i> = −0.154, 95% CI [−0.172, −0.137]). These indirect effects represented 14.60%, 21.50%, and 35.20% of the total effect, respectively.</p> Conclusion <p>This study highlights the chain-mediating role of anxiety and depression in the relationship between symptom clusters and perceived cognitive function in NPC survivors. Effective management of symptom clusters and timely alleviation of anxiety and depression may be associated with the mitigation of perceived cognitive difficulties in this population.</p>