Taken together, our results indicate that FAO inhibition further sensitizes HK1−HK2+ cells to the combined inhibition of glycolysis and the mitochondrial electron transport chain (ETC) and that the triple combination of HK2 inhibition, DPI, and PER simultaneously target the components of multiple energy generation sources (glycolysis, OXPHOS, FAO) in HK1−HK2+ liver cancer cells, resulting in synthetic lethality in cells that express HK2 but not HK1. This evidence concerns the gene PER1 and liver cancer.