〔Abstract〕 Objective To investigate the effects of retinoid-related orphan receptor γ(RORγ) gene on proliferation and metastasis of human colon cancer cells. Methods RORγknockdown cell lines were constructed and the knockdown efficiency was detected by RT-qPCR and Western blot assays; MTT, colony formation, Transwell and wound healing assays were used to detect cell proliferation and metastasis; the expression of epithelial-mesenchymal transition(EMT) related proteins was detected by Western blot. The relationship betweenRORγgene expression and immune cell infiltration in tumor microenvironment was analyzed using TIMER 2.0 database. Results The knockdown ofRORγenhanced the viability(F=157.40,P<0.01), clonogenesis(F=61.35,P<0.01), migration(F=13.00,P<0.01), invasion(F=21.26,P<0.01) and wound healing ability(F=877.2,P<0.01) of colon cancer cells, inhibited the expression of E-Cadherin, and promoted the expression of vimentin and N-Cadherin. TIMER 2.0 database analysis showed thatRORγexpression in colon adenocarcinoma(COAD) tissues was associated with multiple immune cell infiltrates. Conclusion Downregulation ofRORγexpression promoted the proliferation and metastasis of colon cancer cells.