Objective To investigate the efficacy and safety of azacytidine and B-cell lymphoma/leukemia-2 inhibitors in the treatment of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Methods The clinical data of 31 patients with AML/MDS who were clearly diagnosed with AML/MDS were analyzed from 2018.10 to 2021.02, and the total amount of azacyclonol and B-cell lymphoma/leukemia-2 inhibitor was used for single or combined chemotherapy, with a total amount of 75 mg/m 2 ∗ 7 d, divided into 7-10 days of continuous subcutaneous injection, every 28-30 days for a course of treatment. Overall response rate (ORR), median survival, poor response, and genetic mutations were observed. Results A total of 104 courses of treatment were completed in 31 patients, the median course was 3 (1–12), and 6 patients who did not complete 2 courses of treatment were not counted in the statistics. After 2 courses, ORR was 72.0%, CRES was 2 (8.0%), mCR was 16 (64.0%), disease stable was 5 (20.0%), treatment failures were 2 (8.0%), mortality was 40.0%, and median survival time was >5 months. Single-agent and combined ORR was 64.3% and 81.8%, respectively, with median survival of 7.25 and 9 months; ORR for MDS and AML was 66.7% and 76.9%, respectively, median survival of 8 and 11 months was 66.7% and 80.0% of ORRs at 260 and V60 years, respectively, and median survival of 7 and 11.5 months; MDS-EB-1. The ORR of MDS-EB-2 was 75.0% and 62.5%, respectively, with median survival times of 11.5 and 6.5 months. During 2 courses and 4 courses, the rate of transfusion dependence was 64.0% and 55.5%, respectively. Fifteen cases were detected by second-generation sequencing, and the results were 14 cases of combined gene mutations. Conclusion Azacytidine and B-cell lymphoma/leukemia-2 inhibitors have good efficacy and high safety in the treatment of AML and MDS, and the combined treatment is better than that of monotherapy, but the side effects of combination therapy are large.