The present invention relates to a method and a pharmaceutical composition for treating an HCC negative for HBV/HCV, comprising administering a subject in need thereof an therapeutically effective amount of an inhibitory agent to control the genetic alteration of lipid homeostasis associated genes, including CD36 amplification and ABCG4 deletion. According to the present invention, medicines targeting the lipid metabolism pathways are developed to treat HCC patients with CD36 amplification and/or ABCG4 deletion.