Based on the results of isobaric tag for relative and absolute quantification labeling (iTRAQ) and the function of PERK-eIF2α-ATF4-CHOP pathway, we hypothesized that 125I seeds might induce the upregulation of PERK-eIF2a-ATF4-CHOP pathway, resulting in apoptosis in liver cancer cells. This evidence concerns the gene ATF4 and liver cancer.