Objective To analyze the expressions of Gasdermin E (GSDME) and serum amyloid protein A1 (SAA1) in oral cancerous tissues, and to explore their relations with clinicopathological characteristics and prognosis of patients with oral cancer. Methods A total of 102 patients with oral cancer were selected, and GSDME and SAA1 expressions in cancerous tissues and paracancerous tissues were detected by using immunohistochemistry. The expressions of GSDME and SAA1 in oral cancerous tissues of patients with different clinicopathological characteristics were analyzed. The Kaplan⁃Meier method was used to draw survival curve for analyzing the relation of GSDME and SAA1 expressions in cancerous tissues with patients’ prognosis. The multivariate COX regression model was used to analyze the influencing factors for prognosis in patients with oral cancer. Results GSDME expression positive rate in oral cancerous tissues was lower than that in paracancerous tissues, whereas SAA1 expression positive rate was higher than that in paracancerous tissues (P<0.05). Compared with patients with high/medium differentiated degrees, without cervical lymph node metastasis, with TNM stage in Ⅰ-Ⅱ, patients with low differentiated degree, cervical lymph node metastasis, and with TNM stage in Ⅲ obtained a low GSDME expression positive rate in cancerous tissues, and a high SAA1 expression positive rate (P<0.05). The 3⁃year progression⁃free survival rate of patients with GSDME expression negative was lower than that of patients with GSDME expression positive (P<0.05), and the 3⁃year progression⁃free survival rate of patients with SAA1 expression positive was lower than that of patients with SAA1 expression negative (P<0.05). Differentiated degree, cervical lymph node metastasis, TNM stage, GSDME and SAA1 expressions in cancerous tissues were the independent influencing factors for prognosis in patients with oral cancer (P<0.05). Conclusion GSDME expression is decreased, whereas SAA1 expression is elevated in oral cancerous tissues, and both the two as above are closely related to patients' TNM stage, differentiated degree of cancerous cells, cervical lymph node metastasis, and prognosis.