In functional experiments, P4HA2 knockdown combined with radiotherapy not only decreased the expression of cancer stemness markers (e.g., CD44, Oct4) and inhibited sphereforming and migration capacities, but also impaired DNA damage repair and anti-apoptotic abilities by downregulating KU80 and BCL-2 while upregulating γ-H2AX. This evidence concerns the gene P4HA2 and cancer.