Objective: To investigate the efficacy and prognosis of venetoclax combined with hypomethylating agents (HMAs) in the treatment of relapsed/refractory acute myeloid leukemia (AML). Methods: From June 2021 to February 2022, 14 patients with relapsed/refractory AML were treated with venetoclax combined with HMAs, among which nine patients were treated with venetoclax + azacytidine, while five patients were treated with venetoclax + decitabine. The efficacy of the treatments was observed, and the patients were followed up. Results: All patients received one to five courses of treatment, in which the median course of treatment was three; four cases achieved CR and another four achieved PR, with NR in six cases; there was no treatment-related death. There were seven deaths up to the end of the follow-up period, all of which were progressive deaths at the end of the disease, and the overall survival rate was 50.00%. All the patients experienced different degrees of nausea, vomiting, and myelosuppression (Grade II–IV), nine patients had Grade 3–4 hematological adverse reactions, and seven patients had infection. Conclusion: Venetoclax combined with hypomethylating agents is effective in the treatment of relapsed/refractory AML, with good prognosis, and some patients may even achieve CR. Although bone marrow suppression is serious with this combination, it is well tolerated.