Studies have shown that the mRNAs of RAF and ERK are overexpressed of HCC patients.17 Researchers have discovered that cancers are closely related to the Ras pathway, and the major downstream factors of Ras signaling included ERK1/2.18,19 Testis specific protein Y-linked 1 was found to contribute to the up-regulation p-ERK1/2 in RAS signaling pathway.3 Therefore, TSPY1 may enhance the phosphorylation level of key molecules (such as Ras) by activating the related regulatory factors of the ERK1/2 signaling pathway, thereby activating this pathway. Here, MAPK3 is linked to hepatocellular carcinoma.