Objective To evaluate efficacy of morphine sulfate sustained-release tablets and morphine hydrochloride tablets titrated in patients with moderate or severe cancer pain. Methods A total of 140 patients with moderate or severe cancer pain, who had never taken opioid drugs before, were randomized into study group (n=70) and control group (n=70). In the study group, morphine sulfate sustained-release tablets were titrated, and morphine hydrochloride tablets were used during pain evaluation. In the control group, morphine hydrochloride tablets were initially titrated. Both groups were observed for the dose, pain relief rate, adverse effects and changes in Karnofsky Performance Status (KPS). SPSS statistics 21.0 was used for data analysis. According to different date type, t test, rank-sum test or χ² test was used for data comparison between two groups. Results The time to effective pain relief in the study group was significantly shorter than that in the control group (Z=1.985,P=0.047). In 1-3h of titration, pain relief rate of the control group was higher than that of the study group (P<0.05). After 4 hours, pain relief rates were of no significant differences. Severe cancer pains in the first to second day of titration were less frequent in the study group than in control group (P<0.05) and were as frequent in both groups in the third day. Medication frequency was lower in the study group than in the control group (P<0.05) in the first day and was the same in both groups after the first day (P>0.05). The common adverse reactions were nausea, vomiting, constipation, dizziness, drowsiness, and dysuria in both groups without significant difference between two groups (P>0.05). Karnofsky performance status(KPS) was not significantly different between two groups from the first to third day (P>0.05) but was improved on the previous day in each group (P<0.05). Conclusion Morphine sustained-release tablets used for initial titration was no worse than morphine ready-release tablets and was worth being used for cancer pain.