In oncology, pain control is a persistent problem. Significant barriers to cancer pain management are patient related. Pain self-management support interventions have shown to reduce pain intensity and patient-related barriers. Comparative effectiveness research is a suitable approach to test whether effects are sustained in clinical practice. In this pilot randomized controlled trial, the implementation of the ANtiPain intervention into clinical practice was tested to assess the effects on pain intensity, function-related outcomes, self-efficacy, and patient-related barriers to pain management to prepare a larger effectiveness trial. Within 14 months, 39 adult oncology patients with pain scores of 3 or higher on a 10-point numeric rating scale were recruited in an academic comprehensive cancer center in Southern Germany. Patients in the control group (n=19) received standard care. Patients in the intervention group (n=20) received ANtiPain, a cancer pain self-management support intervention based on 3 key strategies: provision of information, skill building, and nurse coaching. An intervention session was performed in-hospital. After discharge, follow-up was provided via telephone calls. Data were collected at baseline and 1 and 6 weeks after discharge. Effect sizes were calculated for all outcomes. Large effects were found for activity hindrance (Cohen d=0.90), barriers (d=0.91), and self-efficacy (d=0.90). Small to moderate effects were found for average and worst pain (Cohen d=0.17-0.45). Key findings of this study involved function-related outcomes and self-efficacy. Because these outcomes are particularly meaningful for patients, the integration of ANtiPain to routine clinical practice may be substantial. A larger study will be based on these findings.