〔Abstract〕 Objective To investigate the expression and molecular mechanism of dickkopf 1(DKK1) in tongue squamous cell carcinoma(TSCC) by bioinformatics method and molecular biology experiments. Methods The patients information wasdownload from TCGA-TSCC database,the differentially expressed genes between the cancer and normal tissues were screened by Network Analysed site,the key genes and clinical prognosis were identified through Kaplan-Meier analysis and Lasson regression,the functions and pathways of differentially expressed genes were gained by GO and KEGG database,the expression of DKK1 mRNA and protein in TSCC as well as its relationship with clinicopathological features were analyzed by UALCAN database and immunohistochemistry. Western blot assay was conducted to detect the protein expression of DKK1 in TSCC cells,and siRNA was used to konck down the expression of DKK1 protein in Cal27 cells. Results The three key genes DKK1,CYP19A1 and IRX4,which were highly expressed in tongue squamous cell carcinoma and the survival rate of TSCC patients with high expression group was poor,were screened through Network Analysed,Kaplan-Meier analysis and Lasson regression method. UALCAN database showed that the mRNA level of DKK1 in TSCC tissues was higher than that in normal tissues,and its high expression was significantly correlated with clinical stage,histological grade and lymph node metastasis of TSCC patients. The immunohistochemistry assay suggested that the positive rate of DKK1 protein in clinical stage Ⅲ + Ⅳ TSCC tissues was significantly higher than that in stage Ⅰ + Ⅱ TSCC tissues. In addition,the expression level of DKK1 protein in TSCC tissues was significantly higher than that in adjacent tissues. Western blot assay also showed that the protein expression of DKK1 in TSCC cell Cal27 was much higher than normal oral epithelial cell HOEC. When knock down the protein expression of DKK1 in Cal27,the expression of β-catenin、pp65 和 p65 werealso reduced. Conclusion DKK1 is highly expressed in tongue squamous cell carcinoma tissues and cells and plays an important role. It may be a new target for early diagnosis and drug treatment of TSCC.