Background: Pain is one of the most common concomitant symptoms among cancer patients. Pharmacologic agents are regarded as a cornerstone of cancer pain management. 'Dose titration' with short-acting morphine is widely accepted. Such a titration method is very complicated. The analgesic background establishment is often delayed. Titration based on sustained-release opioids is also recommended, but the onset of analgesic effect requires hours, whereas the rescue analgesia is always needed. This study evaluated the optimized morphine titration scheme with a simultaneous combination of sustained-release morphine and subcutaneous morphine. Methods: In a multicenter, 7-day, randomized controlled study, patients with moderate to severe cancer pain were assigned to receive either sustained-release morphine and subcutaneous morphine simultaneously (rapid titration) or only subcutaneous morphine to dose titration. The primary outcome was the safety and the number of times of rescue therapy as needed in the first 24 h. Results: A total of 108 patients with moderate to severe cancer pain were included in the study. The number of times of rescue analgesics in the first 24 h significantly reduced in the rapid titration group (0.4 +/- 0.48 vs. 2.3 +/- 0.78, P = 0.000). No differences in the intensity of opioid-related symptoms were found between the two groups. Conclusions: Rapid titration is safe and efficient, which could significantly decrease rescue analgesics in the first 24 h and achieve better analgesic efficacy for cancer pain patients.