Background: Cancer patients can experience both physical and non-physical problems such as psychosocial, spiritual, and emotional problems, which impact the quality of life. Previous studies on quality of life mostly have employed multivariate analyses. To our knowledge, no studies have focused yet on the underlying causal relationship between factors representing the quality of life of cancer patients, which is very important when attempting to improve the quality of life. Objective: The study aims to model the causal relationships between the factors that represent cancer and quality of life.Methods: This study uses the S3C-Latent method to estimate the causal model relationships between the factors. The S3C-Latent method combines Structural Equation Model (SEM), a multi objective optimization method, and the stability selection approach, to estimate a stable and parsimonious causal model.Results: There are nine causal relations that have been found, i.e., from physical to global health with a reliability score of 0.73, to performance status with a reliability score of 1, from emotional to global health with a reliability score of 0.71, to performance status with a reliability score of 0.82, from nausea, loss of appetite, dyspnea, insomnia, loss of appetite and from constipation to performance status with reliability scores of 0.76; 1; 0.61; 0.76; 0.72; 0.70, respectively. Moreover, this study found that 15 associations (strong relation where the causal direction cannot be determined from the data alone) between factors with reliability scores range from 0.65 to 1.Conclusion: The estimated model is consistent with the results shown in previous studies. The model is expected to provide evidence-based recommendation for health care providers in designing strategies to increase cancer patients’ life quality. For future research, we suggest studies to include more variables in the model to capture a broader view to the problem.