Many under-expression gene sets between schizophrenia and hepatocellular carcinoma genes are noted, including CD4-CXCL12-DPP4, HLA-DPA1-CD4-FCGR3-PTPRC, MYO1C-ESR1-RARA, FOS-JUN-EGR1, etc. Moreover, the combination of over- and under-expression level genes of both diseases such as CASC5-ZWINT, MARCO-SCGB3A2, PLD1-PEA15, GTF3C3-POLR3C, TBCE-TBCD-XRCC6, etc.(pink region) highlight the potential biological significance of gene set combination implicating the protective factor for both diseases. The gene discussed is ESR1; the disease is hepatocellular carcinoma.