We aimed to develop a prognostic nomogram based on immunohistochemistry (IHC) biomarkers of patients with oral squamous cell carcinoma (OSCC). A total of 294 patients were enrolled in the study. The least absolute shrinkage and selection operator (LASSO) Cox regression model was performed to develop a combined IHC score (IHCs) classifier. Five biomarkers, specifically c-Met, Vimentin, HIF-2α, VEGF-c, and Bcl-2 were extracted. Then, an IHCs classifier was developed, and patients were stratified into high- and low-IHCs groups. In the training cohort, the 5-year overall survival (OS) was 62.1% in low-IHCs group and 28.2% in high-IHCs group (<0.001). The 5-year OS was 68.6% for the low-IHCs group and 28.4% for the high-IHCs group in the validation cohort (<0.001). The area under the ROC curve (AUROC) of the combination of the IHCs classifier and TNM stage was 0.746 (95% CI: 0.658-0.833) in the training cohort and 0.735 (95% CI: 0.651-0.818) in the validation cohort, respectively. The nomogram could effectively predict the prognosis for patients with OSCC and may be employed as a potential tool to guide the individual decision-making process.