Abstract: Objective The aim of this study was to investigate the effects of problem-solving therapy(PST)on depression and quality of life in patients with advanced hepatocellular carcinoma(HCC)undergoing immune checkpoint inhibitor(ICI)therapy,and to analyze its potential effect on the efficacy and survival outcomes of immunotherapy,providing practical evidence for constructing a comprehensive treatment model for patients with advanced HCC that integrated physical and psychological therapies. Methods A single-center,prospective,randomized controlled trial was conducted.Patients with advanced HCC who were undergoing ICI therapy for the first time and had depressive symptoms were enrolled and randomly assigned in a 1∶1 ratio to the control group(n=53)and the experimental group(n=53).The primary outcome measure was depression score,and secondary outcome measures included objective response rate(ORR),disease control rate(DCR),overall survival(OS),progression-free survival(PFS),and quality of life score.On the basis of conventional treatment,the control group received supportive psychological intervention,while the experimental group underwent PST in addition to the control group′s treatment.Depression and quality of life were evaluated at T0(baseline,one day before intervention),T1(end of the 4th week of intervention),T2(end of the 8th week of intervention),and T3(16 weeks after the end of intervention).Subsequently,patients were followed up every three months for the efficacy and survival. Results There were no statistically significant differences in baseline characteristics between the two groups(P＞0.05).Depression scores at T1,T2,and T3 were lower than those at T0 in two groups,showing a downward trend,and the decrease was more pronounced in the experimental group than that in the control group,with statistically significant differences(P＜0.05).Quality of life scores at T1,T2,and T3 were higher than those at T0 in two groups,showing an upward trend,and the increase was more pronounced in the experimental group than that in the control group,with statistically significant differences(P＜0.05).The follow-up until November 2025 showed that the DCR in the experimental group was significantly higher than that in the control group(92.45% vs. 71.70%,P=0.005),but there was no significant difference in ORR(33.96% vs. 22.64%,P=0.196).Survival analysis results indicated a statistically significant difference in short-term OS(＜12 months)between the two groups(P=0.006),with a higher OS within 12-month in the experimental group compared to the control group;However,there was no statistically difference in short-term PFS(＜6 months)between the two groups(P=0.087). Conclusion PST can alleviate depression in patients with advanced liver cancer,improve their quality of life,and enhance the immunotherapy benefits,and 1-year survival rate in some patients,but its underlying mechanism remains to be further investigated.

Key words: hepatocellular carcinoma, problem-solving therapy, depression, immunotherapy, quality of life, randomized controlled trial