Microarray data is used to screen the genes of oral squamous cell carcinoma (OSCC). Microarray data of OSCC and normal tissues were downloaded from GEO database and analyzed with Benjamini-Hochberg (BH) method. Differentially expressed genes (DEGs) were then uploaded on DAVID database to process enrichment analysis. Target genes were finally chosen for verification experiment in vitro and in vivo. 78 DEGs were selected from 54676 genes, including 46 up- and 32 down- regulation. GO term showed that these genes were related to epidermal growth (biological processes), extracellular region (cellular components) and cytokines activity (molecular function). Protein network interaction demonstrated that OSCC was closely allied to the five key genes including CXCL10, IFI6, IFI27, ADAMTS2 and COL5A1, which was consistent with the RT-PCR data. High-expressed gene CXCL10 was chosen for further cell experiment, and the results indicated that CXCL10 can promote the proliferation, migration and invasion of normal cells and inhibited the cancer cells after si-RNA transfection. Moreover, it has been proven that CXCL10 was possibly related to the occurrence and development of OSCC. Understanding the regulation of OSCC expression will shed light on the screening of cancer biomarker.