OBJECTIVE: To evaluate the safety and efficacy of Tongkuaixiao ointment (TKXO) in treating moderate-to-severe cancer induced somatalgia. METHODS: Totally 130 patients with moderate to-severe cancer induced somatalgia were randomly divided into a TKXO group and a control group. The patients were treated with either TKXO applied externally or placebo, with opioid analgesics orally at the same time. Observation parameters were included numerical rating scale (NRS) scores, analgesic efficacy, initiation effective time, persistent analgesic time, equivalent morphine dose, National Comprehensive Cancer Network (NCCN) grade in Impact of Pain Measurement Scores, and safety and satisfaction extent investigation. RESULTS: NRS scores and NCCN grade in Impact of Pain Measurement Scores decreased significantly after 5-days treatment in the two groups (P < 0.0001). Compared to the control group, initiation effective time was significantly shorter (P < 0.05) and persistent analgesic time was significantly longer (P < 0.01), equivalent oral morphine doses of the first day and the whole treatment course were significantly decreased in the TKXO treatment group (P < 0.01 or P < 0.05). No obvious adverse effects were found in the TKXO group. CONCLUSION: TKXO combined with opioid analgesics possesses the advantages of high efficacy, fast action, long persistent action, safety and convenience in use, and it can reduce the dose of opioid. (C) 2016 JTCM. All rights reserved.