To explore whether the cell surface GRP78 plays a role in the invasion of hepatocellular carcinoma cells, we neutralized the cell surface GRP78 using the N-20 antibody, which has been demonstrated to block the signaling transduction downstream of the cell surface GRP78 effectively in many human cancers, in SMMC7721 and Mahlavu cells and examined the adhesion and invasion status. This evidence concerns the gene HSPA5 and cancer.