Hepatocellular carcinoma (HCC) is a kind of cancer with extremely high mortality. Most patients have been in the advanced stage when they went to see the doctor. The enzyme methionine adenosine transferase (MAT), as the key to the survival of the cell, could promote the biosynthesis of the biological methyl donor S-adenosylmethionine (SAMe) by catalyzing the binding of methionine and adenosine triphosphate (ATP). There is a dynamic equilibrium between MAT1A and MAT2A in normal hepatocytes, which maintains the homeostasis of SAMe. The transformation of MAT1A to MAT2A will reduce the biosynthesis of SAMe and provide favorable conditions for the cell growth of HCC. Generally speaking, MAT1A expression is high but MAT2A expression is low in healthy liver tissues while MAT1A is decreased but MAT2A increased in HCC. Therefore, to accelerate the transformation of MAT2A to MAT1A, then improve the MAT1A/MAT2A ratio would be as a key to HCC treatment. This article mainly discusses the transformation of MAT1A to MAT2A in HCC, aiming to find a new way to explore the target for HCC prevention and treatment.