Through cytometry by time of flight (CyTOF), flow cytometry, and further experiments, Deltex E3 ubiquitin ligase 2 (DTX2) in HCC cells is identified to promote the infiltration and polarization of tumor‐associated neutrophils (TANs) with a protumor phenotype, thus attenuating the infiltration and cytotoxicity of CD8+ T cells partially through C‐X‐C motif chemokine 2 (CXCL2) and C‐X‐C motif chemokine 6 (CXCL6). This evidence concerns the gene DTX2 and neoplasm.