Objective To observe and compare the analgesic effect and safety of hydromorphine-controlled intravenous analgesia (PCIA) titration therapy and morphine hydrochloride tablets in the treatment of severe cancer pain. Methods: 72 patients diagnosed with severe cancer pain (NRS≥7 points) who were admitted to our hospital from June 2022 to June 2024 were selected as the research subjects. The patients were divided into the control group and the experimental group according to the random number table method, with 36 cases in each group. The control group was treated with oral morphine hydrochloride tablets. The experimental group was treated with hydromorphinone PCIA. The treatment conditions (stable pain dose, maintenance dose, onset time, duration), analgesic effect (NRS score, pain relief rate), quality of life score (QOL-30), and the incidence of adverse reactions of the two groups were analyzed and compared. Results: The stable recorded dose of pain in the experimental group was significantly lower than that in the control group, and the average daily maintenance dose was significantly lower than that in the control group (P<0.05). The onset time of the drug from the first administration to the stable control of pain in the experimental group was significantly shorter than that in the control group, and the duration of drug efficacy was significantly longer than that in the control group (P<0.05). Three days after treatment, the NRS scores of both groups were significantly lower than those before treatment, and the NRS score of the experimental group was significantly lower than that of the control group after treatment (P<0.05). The pain relief rate of the experimental group was significantly higher than that of the control group (P<0.05). After treatment, the QOL-30 scores of both groups increased significantly compared with those before treatment, and the QOL-30 score of the experimental group after treatment was significantly higher than that of the control group (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: Hydromorphine PCIA titration has a more efficient and stable analgesic effect than oral morphine hydrochloride tablets. It can effectively reduce the pain degree of patients with severe cancer pain, improve the quality of life, and has higher safety.