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Cancer makes various changes in quality of life and identifying the influential components in this variable can significantly influence patients' quality of life. This study aimed to investigate the structural association between integrative self-knowledge, perception of suffering and quality of life regarding cancer patients. This research was a correlational study and participants were 340 patients selected via available non-random sampling from Karaj medical centres. Patients completed the quality of life (sf-36), self-knowledge and perception of suffering questionnaires. Data were analysed using structural equations model (LISREL) version 8.5 and SPSS version 19. The results showed that there was a significant relationship between integrative self-knowledge and physical suffering, psychological suffering and existential suffering with patients' quality of life. Moreover, the equation-structural relationship between integrative self-knowledge with the components of perceiving suffering and quality of life were significant. In other words, integrative self-knowledge can predict quality of life in the case of cancer patients directly with the meditating role of physical and existential suffering. Fitness indices showed that the proposed model is suitable for explaining the quality of life through the variables of integrative self-knowledge and perception of suffering. Integrative self-knowledge has significant effects on people's cohesiveness and psychological integrity and has a significant impact on improving the quality of life of patients by affecting how they perceive suffering.