In order to evaluate the efficacy and tolerability of oxycodone in moderate-severe cancer-related pain, we conducted a systematic review of randomized controlled trials (RCTs). Publications addressing the efficacy and tolerability of oxycodone in moderate-severe cancer-related pain were selected from the Cochrane library, PubMed, Embase and CBM databases. Data were extracted from the studies by two independent reviewers. The meta-analysis was performed by RevMan 5.0.25 and STATA 9.2 software. From these data, odds ratios (ORs) or the standard mean difference (SMD) with 95% confidence intervals (CIs) were calculated. Finally, only seven RCTs were retrieved with a total of 613 cancer patients with moderate-severe pain. The meta-analysis results showed that oxycodone was statistically superior to other strong opioids based on pain intensity scores following intervention [weighted mean difference (WMD), 0.25; 95% CI, 0.05-0.45; P=0.01; WMD, -1.30; 95% CI, -1.55-1.05; P<0.001, respectively]. In addition, there were statistically significant differences between oxycodone and other strong opioids in cancer-related pain on the obvious effective rate and the overall effective rate (OR, 2.03; 95% CI, 1.40-2.95; P=0.0002; OR, 1.94; 95% CI, 1.09-3.44; P=0.02, respectively). Compared with other strong opioids, nausea and constipation occurred significantly less frequently with the use of oxycodone for cancer-related pain (OR=0.52, 95% CI=0.32-0.85, P=0.009; OR= 0.55, 95% CI= 0.35-0.87, P= 0.01; respectively). In conclusion, this meta-analysis confirms that the efficacy and tolerability of oxycodone are superior to those of other strong opioids, including morphine sulfate, codeine and tramadol, supporting its use as an opioid for cancer-related pain.