Abstract: Objective To investigate the expression of Notch1 receptor and EGFR in tongue squamous cell carcinoma and analyze the potential relationship between Notch1 and EGFR. Methods A total of 71 cases of TSCC and 62 cases of tongue leukoplakia specimens and 17 cases of normal tongue mucosa specimens from January 2010 to December 2014 in our hospital were collected as study subject.The Notch1 and EGFR expression of three groups were determined by immunohistochemical method,and the results of three were statistically analyzed by SPSS 16.0. Results The Notch1 expression in normal tongue mucosa and tongue leukoplakia specimens were mainly in the horny layer and no expression in base layer.While the EGFR expression in normal tongue mucosa and tongue leukoplakia specimens were mainly in base layer and expression in horny layer and granular layer.In TSCC,Notch1-positive cell ratio of high degree specimens was higher(P<0.05) and Notch1-positive cell ratio of higher TNM stage,tongue myometrial invasion and lymph node metastasis were lower(P<0.05).While the EGFR-positive cell ratio of high degree specimens was lower(P<0.05) and EGFR-positive cell ratio of higher TNM stage,tongue myometrial invasion and lymph node metastasis were higher(P<0.05). Conclusion Notch1 receptor expression can result in the cell differentiation of tongue epithelium,and the reduction of Notch1 receptor expression can result in the inhibition of tongue epithelium.EGFR expression can inhibit the Notch1 expression,and they might have an interaction effect in the development of squamous cell carcinoma.