Background: The aim of this study was to assess EGFR and p53 expression in head and neck tumors among Sudanese patients using immunohistochemistry. Materials and Methods: A retrospective descriptive study was performed on 150 samples from patients diagnosed with HNCs as well as 50 from individuals with benign head and neck tumors. EGFR and p53 expression was assessed using immunohistochemistry (IHC). Results: EGFR was expressed in 126/150 (84%) of HNCS and 6/50 (12%) benign head and neck tumors where as p53 was expressed in 29/150 (19.3%) of HNCs and 2/50 (4%) of benign head and neck tumors, with significance at p values of 0.001 and 0.009 respectively. Conclusions: There is a significant association between EGFR, P53 expression and head and neck cancers among Sudanese patients.