Background. TP53 is a very common tumor suppressor gene and has implicated in various cancers. A systematic immunological analysis of TP53 somatic mutation classification in multiple cancers is still lacking. Methods. To assess the immunological value of TP53 somatic mutation classification in various cancers, we integrated a series of bioinformatics methods to analyze the role of TP53 gene across the public databases, such as UCSC Xena, Cancer Cell Line Encyclopedia (CCLE), Ensembl, and Genotype−Tissue Expression (GTEx). Results. The results revealed that the TP53 expression level had significant difference in tumor tissues and normal tissues, and it had a high expression level in most malignant tumors. Moreover, the missense mutation is the most common type of TP53 mutation in most cancers. In addition, the Cox proportional hazards model analysis and Kaplan−Meier (KM) survival analysis demonstrated that the TP53 expression is a high-risk factor in brain lower-grade glioma (LGG), prostate adenocarcinoma (PRAD), and uterine carcinosarcoma (UCS), which is opposite in uterine corpus endometrial carcinoma (UCEC). Besides, compared to the TP53 nontruncating mutation classification samples, we found that TP53 truncating mutation samples had lower TP53 expression levels in certain types of cancer. Notably, TP53 was associated with the mismatch repair (MMR) gene in some cancers which contained truncating or nontruncating mutation. Based on the classification of truncating or nontruncating mutation, we also discovered that TP53 expression was positively or negatively correlated with the immune score, stromal score, and the levels of immune cell infiltration in different cancers. Conclusions. Our research reveals an overarching landscape of immunological value on TP53 status in various malignant tumors. According to our results, we demonstrate that TP53 also plays an immunological role in various cancers.