Background: Music-based intervention is commonly used as a non-pharmacological strategy to reduce pain in hospitalized patients. Purpose: To conduct a systematic review and meta-analysis to examine the effects of passive music-based interventions on pain relief in cancer patients undergoing diagnostic biopsies and surgeries and to identify the moderating variables in order to identify clinically validated interventional strategies and related suggestions. Methods: Studies using an RCT (randomized clinical trial) design that were published before 2016 were collected from the following databases: Cochrane Library/Trials, PubMed, PsycINFO, CINHAL, and Index to Taiwan Periodical Literature System. The high-quality studies, defined as those earning a modified Jadad scale score > 3, were then analyzed using comprehensive meta-analysis software. Results: The passive music-based interventions had a small-to-moderate overall effect (g = -.42, p = .02) on pain relief in the subjects undergoing diagnostic biopsies and surgery in the analyzed studies (n = 12). Subgroup analysis identified the moderating variables affecting pain reduction as the type of anesthesia administered and the settings, frequency, and music therapist that were used in the intervention. Conclusion/Implications for Practice: Passive music-based interventions have a significant pain reduction effect and may be used as an effective, non-pharmacologic intervention for cancer patients undergoing diagnostic biopsies and surgery. Delivering 2-3 intervention sessions daily, using a certificated music therapist to deliver/guide the sessions, holding the sessions in waiting-room or ward settings, and administering a general anesthesia were identified as the crucial factors impacting the effectiveness of music intervention on pain relief.