Background: Patients with head and neck cancer (HNC) have to cope with a multitude of treatment-related adverse effects that impact their quality of life (QoL) post-treatment completion. The presence of family resilience could potentially foster individual resilience and might contribute to patients’ QoL. However, this interconnection has not been confirmed. Objective: To explore the relationships between family resilience, individual resilience, and QoL in patients with HNC and to determine whether individual resilience in HNC patients functions as a mediator between family resilience and QoL. Methods: From September 2022 to June 2023, a cross-sectional survey was conducted among 185 patients with HNC recruited through convenience sampling from a tertiary care hospital in Jiangsu Province, China. Self-report measures of family resilience, individual resilience, and QoL were assessed. Relationships were examined by Pearson’s correlations. Structural equation models were used to assess whether individual resilience played a mediating role between family resilience and QoL. Results: There were significant positive correlations between QoL and both family resilience ( r = 0.43, P < .01) and individual resilience ( r = 0.59, P < .01). Moreover, family resilience had an indirect influence on QoL through its effect on individual resilience (β = 0.319, 95% CI: 0.336-0.815). Conclusion: Family resilience emerges as a significant positive factor capable of enhancing QoL for patients with HNC by bolstering their resilience. To mitigate the detrimental effects of inadequate individual resilience on QoL of patients with HNC, it is advised to implement interventions focused on enhancing family resilience. China Clinical Trials Registry number: ChiCTR2300067612