In the present study, we found that: (1) LicA inhibits the migration and invasion of HCC cells, and does not exhibit any significant toxicity in normal hepatic cells; (2) LicA inhibits the expression and activity of uPA in HCC cells; (3) LicA inhibits the activities of MKK4 and JNK in HCC cells; and (4) LicA suppresses uPA via an inhibition of the MKK4/JNK signaling pathway, exert inhibitory effects on the nuclear translocation of the transcription factor NF-κB and its binding to uPA promoter, reduce the levels of uPA and then have an antimetastatic effect. The gene discussed is MAPK8; the disease is hepatocellular carcinoma.