Objective: To investigate the effect of lidocaine on proliferation and apoptosis of pediatric acute myeloid leukemia cells and its mechanism. Methods: Acute myeloid leukemia cell line HL-60 and K562 was treated with lidocaine at a final concentration of 0.2 mmol/L, 0.5 mmol/L, 0.75 mmol/L, respectively, and normal cells without any treatment were used as control (Con) group; si-NC, si-STAT3 was transfected into HL-60 cells, recorded as si-NC group, si-STAT3 group; pcDNA3.1, pcDNA3.1-STAT3 was transfected into HL-60 cells and treated with 0.5 mmol/L lidocaine recorded as LID 0.5 mmol/L + pcDNA3.1 group, LID 0.5 mmol/L + pcDNA3.1-STAT3 group; all transfections were performed by liposome method. Protein expression was detected by Western blot; cell proliferation was detected by MTT assay; apoptosis was detected by flow cytometry. Results: Lidocaine inhibits the expression of CyclinD1 and Bcl-2, promotes the expression of p21 and Bax, inhibits the proliferation of HL-60 and K562 and promotes apoptosis. Lidocaine also inhibits the expression of STAT3, and inhibition of STAT3 expression can inhibit the proliferation of HL-60 and promote cell apoptosis. Overexpression of STAT3 reversed the proliferation inhibition and apoptosis-promoting effects of lidocaine on HL-60 cells. Conclusion: Lidocaine can inhibit the proliferation of HL-60 and K562 cells and promote cell apoptosis. The mechanism may be related to the regulation of STAT3. It will provide new ideas and new targets for the treatment of acute myeloid leukemia.