An ERK inhibitor (10 μM SCH772984) or JNK inhibitor (25 μM SP600125) repressed the upregulated LAGE3-induced proliferation, migration, and invasion of HCC cells.<h4>Conclusions</h4>LAGE3 enhanced the malignant phenotypes of HCC by promoting the JNK and ERK signaling pathway. Here, MAPK8 is linked to hepatocellular carcinoma.