〔Abstract〕 Objective To study the new target and molecular mechanism of E3 ubiquitin ligase Ring finger 43(RNF43) in human gastric adenocarcinoma cell AGS. Methods The transfection efficiency of RNF43 in AGS cell was observed by fluorescence microscopy; the potential interaction between RNF43 and endogenic phosphates and tensin homologue deleted on chromosome ten(PTEN) in cancer cells was analyzed by Western blot; the specific interaction between RNF43 and PTEN and the ubiquitination of PTEN by RNF43 was verified by CO-IP; the apoptosis, proliferation and migration ability of gastric cancer cells was determined by flow cytometry, CCK-8 assay and scratch test. Results Cytofluorescence results showed that exogenous RNF43 was successfully overexpressed in AGS cells; RNF43 interacts with PTEN in AGS cells, and RNF43 could ubiquitinate PTEN through K63 ubiquitination and increase the protein of PTEN expression level. The results of cell function experiments showed that RNF43 could accelerate the apoptosis of AGS and inhibit the proliferation and migration of AGS by targeting and regulating the functional level of PTEN. Conclusion RNF43 inhibits the proliferation of AGS cellviaits functionality of ubiquitination towards PTEN.