Introduction: Cancer is among the most prevalent chronic diseases in recent decades, exerting a profound impact on multiple aspects of the lives of patients and their families. 
Aim: This study aimed to examine a causal model of quality of life based on the sense of coherence, with the mediating role of pain anxiety in cancer patients.
Method: This applied and descriptive study, employing structural equation modeling (SEM), was conducted among cancer patients attending oncology clinics in Sanandaj, Iran, during the fall of 2023. A convenience sampling method was utilized, and the required sample size was determined to be 186 using G*POWER software, with a significance level of α = 0.05 and a statistical power of 0.90. Data were collected using standardized questionnaires assessing quality of life, pain anxiety, and sense of coherence. Statistical analysis was conducted using AMOS software.
Results: Results showed that the sense of coherence had a positive and significant impact on quality of life (β = +0.218, p ≤ 0.001). Pain anxiety had a negative effect on quality of life (β = -0.414, p ≤ 0.001), and the sense of coherence negatively influenced pain anxiety (β = -0.344, p ≤ 0.001). Furthermore, the mediating role of pain anxiety in the relationship between sense of coherence and quality of life was significant (β = -0.180, p ≤ 0.001). The model's goodness-of-fit index was 0.223, indicating moderate fit.
Conclusion: Enhancing the sense of coherence can improve the quality of life in cancer patients by reducing pain anxiety. Therapeutic interventions should focus on strengthening the sense of coherence and alleviating pain anxiety to improve patients' overall well-being.