Objective: To understand the immune molecular landscapes of the two major costimulatory and coinhibitory pathways (B7 and TNFR families) in oral squamous cell carcinoma. Methods: The B7 family members (CD80, CD86, CD274, ICOSLG, CD276, VTCN1, NCR3LG1, HHLA2 and PDCD1LG2) and TNFR family members (TNFSF4, CD40, CD70, TNFSF9, TNFRSF14 and TNFSF18) were used to analyse the costimulatory and coinhibitory pathway alterations in oral squamous cell carcinoma. The online tools UCSC Xena and cBioPortal were used to derive oral squamous cell carcinoma patients' clinical parameters, mRNA levels, mutations, DNA copy number alterations and methylation levels. The correlations between mRNA levels and methylation levels were determined using Spearman's correlation analysis. A Kaplan-Meier survival analysis was performed to examine the relationships between mRNA expression levels and overall survival. Results: Compared with normal oral epithelial tissues, approximately 23.1% of patients showed upregulation of B7 expression and 15.3% showed upregulation of TNFR expression in oral squamous cell carcinoma, with CD274 (PD-L1) upregulation being the most common alteration. Mutations and copy number alterations were shown to have little effect on B7 and TNFR expression. The mRNA levels of B7 and TNFR genes were negatively correlated with their methylation levels. Furthermore, oral squamous cell carcinoma patients with high expression levels of CD274 showed poor overall survival, while those with high expression levels of CD276 or HHLA2 showed good clinical outcomes. Conclusion: This study elucidated the molecular landscapes of the B7 and TNFR genes in oral squamous cell carcinoma, which could provide a novel strategy for clinical therapy. Keywords: B7, genomic alteration, oral squamous cell carcinoma, survival, TNFR