OBJECTIVES:  Health-Related Quality of Life (HRQoL) is critical to cancer patients in terms of care, making treatment decisions and survival. This study aims to measure HRQoL among cancer survivors stratified by opioid exposure in the United States. METHODS:  Data were obtained annually from 2008-2013 using Medical Expenditure Panel Survey (MEPS). Cancer survivors were identified using survey questions and clinical classification codes excluding non-melanoma skin cancer. The HRQoL was measured in terms of physical component summary (PCS) and mental component summary (MCS) scores using Short Form-12. The HRQoL among cancer survivors with opioid exposure were reported for the following classes: (a) with any opioid use (opioids, narcotic analgesic combinations), (b) no opioid use but at least one prescription for other pain medication (adjuvant analgesics and non-opioids such as NSAIDs, salicylates, non-narcotic analgesic combinations) and (c) without pain medication. Data were analyzed using appropriate statistical procedures for the MEPS with its unique sampling design. RESULTS: A total of 23.1 million cancer survivors and 193.5 million individuals without cancer history were identified. The cancer survivors had significantly (p<0.001) lower PCS and MCS scores, 43.9(SE=0.20) and 50.2(SE=0.16) compared to individuals who never had cancer, 50.0(SE=0.07) and 51.2(SE=0.05) respectively. Among cancer survivors, 35.0% had at least one prescription claim for opioids, 18.4% had no prescription for opioids but at least one claim for other pain medication and 46.6% had no prescription for a pain medication. For these three groups the PCS and MCS scores were 39.2(SE=0.31), 43.1(SE=0.42), 47.7(SE=0.23) and 48.1(SE=0.27), 49.7(SE=0.35), 52.0(SE=0.18) respectively. CONCLUSIONS: A high percentage of cancer survivors take opioids for the disease or for treatment. The lower HRQoL scores indicate cancer survivors are in pain and need to be screened appropriately for their physical and psychological concern.