In order to verify the contribution of structural substitutions of EVO in RCC cell apoptosis, PERK activation, and Bcl-2 protein phosphorylation, four EVO-related chemicals, including EVO-1, -6, -7, and -8, were applied in this study, and all chemicals shared the same chemical structure except for different substitutions including a methyl of EVO, an ethyl of EVO-8, a hydrogen of EVO-1 and -6, and a butyl of EVO-7 at position 14. This evidence concerns the gene EIF2AK3 and renal cell carcinoma.