BackgroundOral squamous cell carcinoma is an increasingly prevalent cancer type characterized by high incidence and mortality rates. Its early detection is challenging, primarily because of the absence of early molecular markers. Cuproptosis is a novel regulatory mechanism of cell death with implications in various cancers. In this study, we aimed to study cuproptosis‐related genes in oral squamous cell carcinoma to identify their prognostic value.MethodsBy analyzing genomic, bulk RNA‐seq, and single‐cell RNA‐seq data, we investigated 13 cuproptosis‐related genes in The Cancer Genome Atlas‐Oral Squamous Cell Carcinoma dataset and Gene Expression Omnibus repository (GSE172577).ResultsATP7A, ATP7B, and DLST were the most frequently mutated genes, with nine of our studied genes associated with overall survival. Single‐cell analysis was conducted to identify cuproptosis‐related tumor cells in oral squamous cell carcinoma, which revealed two distinct patterns based on the expression of cuproptosis‐related genes. These patterns exhibit differences in genetic alterations and tumor immune microenvironment. Finally, we developed a cuproptosis index using a random forest algorithm based on cuproptosis pattern‐related genes in which higher levels were linked to poorer prognosis.ConclusionOur findings provide valuable insights into the mechanisms underlying oral squamous cell carcinoma‐associated cuproptosis.