Objective To investigate the effect of the psychological intervention combined with hyperbaric oxygen therapy on the mental status and the quality of life of patients with depression after cerebral stroke.Methods 45 patients with depression after cerebral stroke were randomly divided into the study group (n = 22)and the control group(n = 23). The two groups had the same clinical routine treatments including improving cerebral cirulation, reducing intracranial pressure, drugs to anti-infection, nervous nutrition and corresponding operation for 8 weeks as a course of treatment, and psychological behavior intervention combined with hyperbaric oxygen therapy was added to the study group. The scores of Hamilton depression rating scale (HAMD) on both groups were evaluated before and spitzer' s quality of life index(QL-INDEX) were used and investigated on two groups at the end of 8 weeks. Results There was no significant difference on the scores of HAMD between the two groups before therapy (P ＞ 0. 05). The scores on HAMD of the study group after the treatment notably dropped compared to the control group (P＜ 0. 01). The difference of the scores on group index of quality of life between the study group (8.57 ± 1.94) and the control group (7.30 ± 1.98) had statistical significance (P ＜0. 05). Conclusion Psychological intervention combined with hyperbaric oxygen therapy plays an important role in the treatment of patient with depression after cerebral stroke to improve their mental status, treatment effectiveness and quality of life.