Objective To investigate the targeting relationship between miR-221-5p and aldehyde dehydrogenase-1 family member A2 ALDH1A2 and its effect on proliferation migration invasion and epithelial-mesenchymal transformation EMT of gastric cancer cells. Method Gastric cancer tissues and their adjacent normal tissues were obtained from 50 patients with gastric cancer by radical gastrectomy in Yuechi People's Hospital from July 2020 to July 2022. The cell lines cultured in vitro included human normal gastric mucosal epithelial cell line GES-1 and human gastric cancer cell lines BGC-803 AGS SGC-7901 BGC-823 and HGC-27. The expression of miR- 221- 5p and ALDH1A2 mRNA in tissues and cells was detected by qRT-PCR. The correlation between miR- 221-5p expression and clinicopathological parameters in gastric cancer was analyzed by Pearson test. The targeting regulation of miR-221-5p on ALDH1A2 was verified by bioinformatics prediction and dual luciferase experiment. HGC-27 cells were divided into control group inhibitor-NC group miR- 221 - 5p inhibitor group mimic NC group miR- 221 - 5p mimic group miR- 221 - 5p mimic + pcDNA3. 1 group and miR - 221 - 5p mimic + pcDNA3. 1 - ALDH1A2 group and the corresponding plasmids were transfected. Cell proliferation invasion migration apoptosis and cell cycle distribution were detected by MTT method clone formation test Transwell chamber test scratch test and flow cytometry respectively. The expression of EMT-related proteins in cells was analyzed by Western blot. Result The expression of miR-221-5p was significantly high in gastric cancer tissues and cells while the expression of ALDH1A2 mRNA was significantly down-regulated in gastric cancer tissues P< 0. 05 . The expression of miR- ·69· 肿瘤代谢与营养电子杂志 2023 年 2 月 9 日第 10 卷第 1 期 Electron J Metab Nutr Cancer, Feb. 9, 2023, Vol. 10, No. 1 221-5p was significantly correlated with TNM stage tumor differentiation and lymph node metastasis in patients with gastric cancer P<0. 05 . MiR-221-5p targeted inhibition of ALDH1A2 expression. Compared with anti-miR-NC group the OD value scratch healing rate E-cadherin α-catenin protein expression and the proportion of S phase cells in anti-miR-221-5p group decreased significantly while the expression level of E- cadherin and α - catenin protein and the proportion of G0 / G1 phase cells increased significantly while the number of monoclonal formation and invasion decreased significantly P<0. 05 . The miR-221-5p group of cells obtained the opposite results as described above when compared to the miR-NC group. Up-regulation of ALDH1A2 expression can reverse the effect of miR-221-5p on the malignant biological behavior of HGC-27 cells. Conclusion Overexpression of miR-221-5p may promote proliferation migration invasion EMT and cell cycle progression and inhibit apoptosis of gastric cancer cells through targeted down-regulation of ALDH1A2 expression.