Integrating the significance of prognosis, TIICs, ICP genes, and MSI and (or) TMB, we induced that HMGBs might be promising immunological targets for the following cancers: HMGB1 for ACC and KIRC; HMGB2 for ACC and LGG; and HMGB3 for BRAC, SARC, SKCM, and OV. Here, HMGB3 is linked to adrenal cortex carcinoma.