As　an　important　global　medical　problem,　hepatocellular　carcinoma　(HCC)　has　been　recognized　as　the　most　frequent　primary　liver　cancer　and　a　leading　cause　of　death　among　patients　with　cirrhosis.　Surveillance　of　HCC　using　serum　markers　aims　to　reduce　the　disease-related　mortality　of　HCC.　MUC16　(mucin　16,　also　known　as　carbohydrate　antigen　125,　CA125)　has　been　predicted　as　a　tumor　biomarker　for　many　cancer　types.　Based　on　the　high　frequency　mutation　rate　in　a　database　from　the　Cancer　Genome　Atlas　(TCGA),　we　investigated　the　effects　of　MUC16　knockdown　and　the　regulatory　profile　of　MUC16　in　HepG2　and　Huh7　cell　lines.　Knockdown　of　MUC16　was　conducted　via　siRNA　transfection,　and　the　proliferation　of　cells　was　not　affected　by　CCK8　assay　results.　Moreover,　decreasing　the　expression　of　MUC16　enhanced　the　migration　and　invasion　of　cells,　as　shown　by　wound　healing　and　transwell　assays.　Furthermore,　RNA-seq　was　used　to　investigate　the　effect　of　MUC16　knockdown　on　the　gene　expression　profile　of　HepG2　and　Huh7　cells.　Our　study　demonstrated　the　significant　role　of　MUC16　in　the　inhibition　of　the　migration　and　invasion　of　HepG2　and　Huh7　cells.