Objective To analyze the role and mechanism of PD-L1 in oral cancer metastasis based on TCGA and GEO databases. Methods The expression characteristics and clinical significance of the PD-L1 in oral cancer were analyzed using the TCGA database. PD-L1 mRNA levels were detected by quantitative reverse transcription-polymerase chain reaction (RT-qPCR)in various oral cancer cell lines.CCK-8, scrath test, Transwell migration, and matrigel-invasion assays were employed to assess the effects of PD-L1 on proliferation, migration, and invasion of oral cancer cells. The interaction network between PD-L1 and functional genes in patients with oral cancer was constructed using STRING software and the GEO database, and key pathways were screened by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis.The regulatory relationship between PD-L1 and key genes was validated by RT-qPCR. Results TCGA data revealed that PD-L1 was highly expressed in patients with oral cancer and was correlated with lymph node metastasis (P<0.01). PD-L1 was also highly expressed in oral cancer cell lines and its inhibition significantly inhibited the proliferation, migration, and invasion of Cal27 and SCC25 cells (P<0.05). KEGG analysis indicated that PD-L1 activated the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway by upregulating C-X-C motif chemokine ligand (CXCL) 9 and CXCL10, thereby promoting STAT1 expression to regulate oral cancer metastasis. Inhibition of the JAK/STAT pathway further suppressed the proliferation, migration, invasion, and expression of STAT1, CXCL9, and CXCL10 in Cal27 and SCC25 cells (P<0. 05). Conclusions PD-L1 may promote oral cancer cell proliferation, migration, and invasion by upregulating CXCL9 and CXCL10 to regulate the JAK/STAT pathway and enhance STAT1 expression, ultimately driving oral cancer growth and metastasis.