Conclusion. The 78th single nucleotide polymorphism (SNP) in exon 20 of epidermal growth factor receptor (EGFR) might be a predictor of the clinical course of squamous cell carcinoma of the head and neck (SCCHN), and genetic predisposition could influence the progression of SCCHN in Chinese subjects. Objective. To analyze the clinical significance of EGFR SNP in Chinese SCCHN patients. Materials and methods. Direct sequencing of exons 18–21 was used to analyze somatic mutations of EGFR. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to evaluate the expression level of EGFR. The chi-square test and Kaplan–Meier method were the main statistical methods used to analyze the correlation of the investigated variables and prognostic significance. Results. In analyzing exons 18–21 of EGFR in 96 patients with SCCHN, only one SNP was found in the 78th site of exon 20 and it mostly existed in specimens coming from the hypopharynx. Further statistical analysis showed that among the clinical or histopathologic parameters, the 78th SNP had a close relationship with earlier stage and more localized primary carcinoma, while at present the analysis did not support the proposition that the SNP was an independent prognostic factor.