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Cong Hu,1 Jun Dai,1 Xu Lin,1 Ya Meng,2 Hui Liang1 1The First Department of General Surgery, Zhuhai People’s Hospital, Jinan University, Zhuhai City, Guangdong Province, People’s Republic of China; 2Zhuhai Precision Medicine Research Center, Zhuhai People’s Hospital, Jinan University, Zhuhai City, Guangdong Province, People’s Republic of ChinaCorrespondence: Hui LiangZhuhai People’s Hospital, 79 Kangning Road, Zhuhai City, Guangdong Province, People’s Republic of ChinaTel +86 756-2158341Email JohnnyDr_hu@hotmail.comPurpose: Gastric cancer is one of the most common cancers with high mortality. Emerging evidences show that ribosomal s6 kinase4 (RSK4) may be an anti-oncogene in several types of cancers, while its function in GC is still unclear. In the present study, we investigated the role of RSK4 in GC progression using MGC-803 and HGC-27 cell lines in vitro and in vivo.Methods: The expression of RSK4 in gastric cancer cells was evaluated using RT-qPCR and Western blot analysis. We transfected cells with RSK4 siRNA to reduce the expression of RSK4 and then evaluated the effect of RSK4 on cellular function. MTT and cell cycle assays were used to study its effect on cell growth. Flow cytometry was used to evaluate cell apoptosis. Wound healing and Transwell assays were performed to investigate metastasis. Stable cell lines with or without RSK4 knockdown were constructed with lentivirus and tumor-bearing mice were used to investigate the effect of RSK4 on cancer progression.Results: The results revealed that reduction of RSK4 expression inhibited cell apoptosis and promoted cell proliferation, migration, and invasion. Additionally, RSK4 knockdown promoted tumorigenesis in vivo.Conclusion: Our study demonstrated that RSK4 serves as a tumor suppressor in GC.Keywords: gastric cancer, RSK4, proliferation, apoptosis, migration, invasion