Pain acceptance has been associated with improved physical and psychosocial well-being in chronic non-malignant pain patients. However, its effects are unclear in cancer outpatients with pain. Our aim was to determine whether pain acceptance predicts reduced pain, pain interference with function, anxiety, and depression in cancer outpatients. We recruited 116 outpatients from a tertiary oncology center, with various types of cancer and pain levels. Patients completed the Brief Pain Inventory, the Hospital Anxiety and Depression Scale and the Chronic Pain Acceptance Questionnaire, the latter of which comprises activity engagement and pain willingness. We carried out multiple regression analyses, adjusting for patient characteristics and outcomes. Activity engagement and pain willingness significantly predicted pain interference with function (P=0.033 and P=0.041 respectively). However, only activity engagement predicted anxiety (P=0.001) and depression (P<0.001). These findings support the beneficial role of pain acceptance in patients' functional adaptation to cancer-related pain. Activity engagement in particular, shows promise in fostering psychological well-being. Further studies could confirm its role in reducing anxiety and depression in cancer patients with pain and whether it should be included in cancer pain management interventions. Further studies could confirm its role in reducing anxiety and depression in cancer patients with pain, and whether it should be included in cancer pain management interventions.