Background: Cancer patients undergoing oral chemotherapy are prone to suffer from low medication compliance and poor quality of life. The psychosocial factor of self-efficacy influences medication adherence. However, there is a lack of studies on the relationship between the three in cancer patients taking oral chemotherapy. Objective: This study aimed to explore medication adherence, self-efficacy, and health-related quality of life (HRQOL), examine the relationship among these variables, and determine the predictor of medication adherence. Methods: This cross-sectional study was conducted at a national cancer center in Indonesia from July 2021 to February 2022. Cancer outpatients aged 18 years or older taking oral chemotherapy capecitabine were included. Patients’ socio-demographics, disease, and therapy characteristics were collected from medical records and questionnaires. Adherence, self-efficacy, and HRQOL were measured using self-reported questionnaires. Results: The study included 118 patients. The mean adherence score was 92.11% (SD=6.87%), and 79.67% of patients were adherent. The self-efficacy for appropriate medication use score ranged from 61.54 to 100%, with a mean score of 90.39%. The mean global score for HRQOL was 70.13 (SD=19.01). There was a significant positive correlation between medication adherence and self-efficacy (r=0.410, p< 0.001), self-efficacy and physical, role, and cognitive functional (r=0.185, p<0.05; r=0.197, p< 0.05, r=0.221, p<0.05, respectively). Medication adherence was negatively correlated with global quality of life (r=-0.199, p<0.05). This study did not find a correlation between self-efficacy and global quality of life. Multivariate analysis showed that the significant predictors of medication adherence were higher education, shorter duration of treatment, and higher self-efficacy. Conclusions: These findings provide valuable insights into patterns and correlations of oral chemotherapy adherence, self-efficacy, and HRQOL in cancer patients. Developing a future program is essential to enhancing cancer patients receiving oral chemotherapy’s medication compliance, self-efficacy, and quality of life. © the Authors.