OBJECTIVES: To examine the prevalence of CAM use among Malaysian cancer patients and compare the differences in health-related quality of life (HRQoL) between CAM users and non-users. METHODS: This cross-sectional study was undertaken with 393 patients at the oncology wards of Penang General Hospital, Malaysia. The HRQoL between CAM users and non-users was assessed by using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). RESULTS: The majority (46.1%) of the participants were frequent CAM users. The most common CAM therapies were dietary and nutritional supplements (41.3%), herbal products (30.4%), prayers for health reasons including spirituality (22.8%), traditional Malay therapies (20.11%) and Traditional Chinese Medicines (14.1%). No significant difference was found between functional and symptoms scores among CAM users and non-users. However; global health scores/quality of life was significantly different (P=0.002) between CAM users and non-users. CONCLUSIONS: Patients’ interest in the use of CAM highlights the need of greater health care education in this field. This study provides evidence of CAM use and its overall effects on quality of life scores in a sample of patients with cancer. Patients should be aware of the potential benefits of CAM therapies for cancer. Health care professionals can play their role effectively to encourage patients towards rational use of CAM therapies.