〔Abstract〕 Objective To investigate the effects of zinc finger E-box binding homeobox 1（ZEB1）on the prolifera⁃ tion，migration，and invasion of lung adenocarcinoma H322 cells，as well as its underlying molecular mechanisms. Methods The gene expression characteristics of the transcription factor ZEB1 in lung adenocarcinoma were ana⁃ lyzed using data from the GEO and TCGA public databases. RT-qPCR and Western blotting were employed to mea ⁃ sure mRNA and protein expression levels of ZEB1 in lung adenocarcinoma cell lines（H322，A549，95-D）and normal human bronchial epithelial cells（BEAS-2B）. Lentiviral transduction was utilized to establish stable ZEB1- overexpressing（Oe-ZEB 1）and vector control（Oe-NC）H322 cell lines. Cell proliferation was assessed using CCK-8，colony formation，and EdU assays，while apoptosis was evaluated by Hoechst33258/PI double staining. Wound healing and Transwell assays were performed to examine cell migration and invasion capabilities. Cell cycle distribution was determined by flow cytometry ，and Western blotting was used to analyze protein expression changes in relevant signaling pathways. Results The findings from GEO and TCGA indicated that ZEB1 expres⁃ sion in lung adenocarcinoma varied with tumor malignancy grade. RT-qPCR and Western blot analyses revealed significantly higher ZEB1 expression in lung adenocarcinoma cell lines compared to BEAS-2B cells（P < 0. 05）. Results from the CCK-8，colony formation，EdU，wound healing，and Transwell assays demonstrated that，com⁃ pared with the un-transfected control（Control）group，Oe-ZEB 1 H322 cells exhibited enhanced proliferation，mi⁃ gration ，and invasion capabilities（P < 0. 05）. Hoechst33258/PI double staining and flow cytometry analyses showed that，relative to the Control group，apoptosis was reduced in Oe-ZEB 1 H322 cells（P < 0. 05）. Addition⁃ ally，a decreased proportion of cells in the G1 phase and an increased proportion in the S phase were observed in Oe-ZEB 1 cells，indicating accelerated cell cycle progression. Western blot analysis further revealed that，com⁃ pared with the Control group，Oe-ZEB 1 H322 cells exhibited upregulated expression of N-cadherin，mutant p53 （mutp53），and Cyclin D 1（P < 0. 05），while expression levels of E-cadherin，murine double minute 2（MDM2）， and p21 were downregulated（P < 0. 05）. Conclusion Overexpression of ZEB1 promotes the proliferation，migra⁃ tion，and invasion of lung adenocarcinoma H322 cells and may facilitate cell cycle progression by modulating the MDM2/mutp53/p21 signaling pathway，thereby promoting the transition of cells from the G0/G1 phase to the S phase.