Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor of the ErbB family, which is expressed or highly expressed in a variety of solid tumors, including oral cancers. High EGFR expression has been correlated with tumor size, metastasis and survival. In recent years, EGFR has been considered a promising target for monoclonal antibody therapy. A total of 52 patients with oral squamous cell carcinoma (OSCC) were selected for EGFR and phosphorylated EGFR (p-EGFR) detection. Immunohistochemical staining was performed to evaluate EGFR and p-EGFR expression. Positive EGFR and p-EGFR staining was present in 92.3% (48/52) and 98.0% (51/52) of all cases, respectively. High EGFR and p-EGFR expression was present in 63.4% (33/52) and 69.2% (36/52) of all cases, respectively. EGFR and p-EGFR expression did not correlate with the clinical factors tumor stage, regional lymph node metastasis, or distant metastasis. However, a statistically significant correlation was identified between high EGFR expression and the pathologic factor tumor invasion. As a conclusion, the majority of OSCCs highly express EGFR and p-EGFR, indicating the importance of studying the efficacy of anticancer therapy targeting these signal factors.