Objective To investigate the effect of miR-29a-3p overexpression on IL-22-induced proliferation of HaCaT cells. Methods HaCaT cells were divided into four groups, Cell group, IL-22 group, IL-22 +NC group and IL-22+miR-29a-3p group. The expression level of miR-29a-3p was detected by fluorescence quantitative PCR. Cell viability was detected by CCK8. Apoptosis and cell cycle were detected by flow cytometry. Results Compared with the 0 g/L group, the proliferation rate of HaCaT cells in the 25 μg/L group, 50 μg/L group and 100 μg/L group was increased at 24 h, 48 h and 72 h (F value was 33.27, 36.19, 52.29,respectively, all P<0.000 1). Compared with the 0 μg/L group, miR-29a-3p expression level in HaCaT in 50 μg/L and 100 μg/L groups was decreased (F=129, P<0.000 1), with a decrease of 83% and 80%, respectively. Compared with the IL-22+NC group, proliferation rate of IL-22+miR-29a-3p group was decreased at 24 h, 48 h and 72 h (P value was 0.002 1, 0.001 6, 0.023 1, respectively), total apoptosis rate was increased (6.67±1.06 vs 30.55±1.86, P=0.000 1), cell proportion in G1 phase was increased (P=0.000 1), and the cell proportion in S phase was decreased (P=0.000 1). Conclusion Il-22 can reduce miR-29a-3p expression level in HaCaT, and miR-29a-3p overexpression can inhibit the excessive proliferation induced by IL-22 in HaCaT cells by promoting apoptosis and inducing G1 phase arrest.