Objective To observe and analyze the effects of hyperbaric oxygen combined with local mild hypothermia therapy on the efficacy and prognosis of patients with top of basilar artery syndrome. Methods 80 patients with top of basilar artery syndrome who were admitted to the hospital from June 2016 to June 2017 were selected and divided into observation group (40 cases) and control group (40 cases) according to the random number table method. The two groups were given conventional medical treatment of top of basilar artery syndrome, and control group was given local mild hypothermia therapy, and observation group was treated with hyperbaric oxygen on the basis of control group, and the two groups were treated for 2 w, and all patients were followed up for 6 months after treatment. The nitric oxide synthase, excitatory amino acid, neutrophil count, total effective rate and prognosis were compared between the two groups before and after treatment. Results After treatment, the nitric oxide synthase, excitatory amino acid, neutrophil count and neurological deficit score in observation group were significantly lower than those in control group (P<0.05). The total effective rate in observation group was significantly higher than that in control group. The prognosis in observation group was significantly better than that in control group (P<0.05). Conclusion Hyperbaric oxygen combined with local mild hypothermia therapy can significantly improve the rehabilitation and prognosis of patients with top of basilar artery syndrome.