Herein, for the first time, we found that an aberrant nuclear expression pattern of STEAP3 which promotes HCC cell proliferation by interacting with EGFR and enhancing EGFR-RAC1-ERK-STAT3 and RAC1-JNK-STAT6 signaling, and it could be employed as a novel prognostic marker and/or effective therapeutic target for human HCC. The gene discussed is STAT6; the disease is hepatocellular carcinoma.