This study aimed to describe self-efficacy (SE) for coping with cancer in patients with head and neck cancer and to assess its relationship with patients' quality of life, which will be a guide for interventions to enhance quality of life and improve self-efficacy for coping with cancer in this target population. Between September 2023 and July 2024, 200 patients with head and neck tumors from a tertiary care hospital in Liaoning Province, China, participated in a cross-sectional study. SE for coping with cancer was measured by the Cancer Behavior Inventory (Version 3.0) in Chinese (CBI-V3.0-C). Quality of life was assessed using Functional Assessment of Cancer Therapy-Head & Neck (FACT-H&N). Data were analyzed using a t-test, Pearson correlation analysis, and Multivariate linear analysis. Self-efficacy of seeking and understanding medical information was the highest-ranked subscale while using spiritual coping was the lowest-ranked subscale. Self-efficacy of age, maintaining activity and independence, maintaining a positive attitude, and coping with treatment-related side effects contributed significantly to QoL as measured by FACT-H&N. Self-efficacy for coping with cancer contributes significantly to QoL in patients with head and neck cancer. It is recommended that SE for coping with cancer be evaluated in practice. Considering its contribution to patients' QoL, interventions to improve self-efficacy for coping with cancer need to be sought in future studies.