Loss of USP22 expression delays TNFα/carbobenzoxyvalyl‐alanyl‐aspartyl‐[O‐methyl]‐fluoromethylketone (zVAD.fmk)/Smac mimetic‐induced necroptosis in several human tumor cells, without affecting TNFα‐induced nuclear factor‐kappa B (NF‐κB) signaling or TNFα‐mediated extrinsic apoptosis. Here, USP22 is linked to neoplasm.