To explore the miR-22-3p and miR-149-5p induced difference in expression of MTHFR between HCC cells and normal hepatocytes, the relative expression of MTHFR in hepatocellular carcinoma cells under conditions of FA deficiency was markedly lower in 12% (P<0.05, 7th day), 17% (P<0.01, 14th day) 20% (P<0.01, 21st day) of cells compared with the control. This evidence concerns the gene MTHFR and hepatocellular carcinoma.