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AIM: To investigate the expression of syntaxin binding protein 4 (STXBP4) in oral squamous cell carcinoma (OSCC) and its effects on the malignant biological behavior of OSCC cells. METHODS: (1) The TIMER, GEPIA2, UALCAN, ENCORI, GEO and HPA databases were used to comprehensively study the expression of STXBP4 in head and neck squamous cell carcinoma (HNSCC) tissues at mRNA and protein levels. The mRNA and protein expres⁃ sion levels of STXBP4 in OSCC cell lines were detected by qPCR and Western blot, respectively. (2) The expression of STXBP4 in SCC-9 cells was down-regulated by small interfering RNA (siRNA), and knockdown (si-STXBP4-1, si-STXBP4-2 and si-STXBP4-3) groups and negative control (si-NC) group were established. Overexpression of SCAL-27 cells was achieved by lentivirus transfection, and overexpression (LV-STXBP4) group and negative control (LV-NC) group were established. The viability, colony formation and migration of OSCC cells were examined by CCK-8, plate colony formation, and Transwell assays, respectively. Western blot was used to detect the expression of epithelial-mesen⁃ chymal transition (EMT)-related proteins. (3) By establishing a subcutaneous xenograft tumor model in nude mice, we in⁃ vestigated the effect of STXBP4 on the proliferation of OSCC cells in vivo. RESULTS: (1) Analysis of the TIMER, GE⁃ PIA2, UALCAN, ENCORI and GEO databases revealed that HNSCC tissues had higher STXBP4 mRNA levels than nor⁃ mal tissues. Immunohistochemical staining from HPA database showed that STXBP4 protein in HNSCC tissues was higher than that in normal oral mucosa tissues. In contrast to normal oral mucosa cells, STXBP4 was highly expressed in 5 OSCC cell lines (P<0. 05). (2) The relative expression of STXBP4 in SCC-9 cells transfected with si-STXBP4-1, si-STXBP4-2 and si-STXBP4-3 was significantly lower than that in si-NC group (P<0. 01). Compared with si-NC group, knockdown of STXBP4 resulted in decreased proliferation and migration of SCC-9 cells (P<0. 05). The CAL-27 cells transfected with LV-STXBP4 had considerably higher STXBP4 level than the cells in LV-NC group (P<0. 01), and had markedly better proliferation and migration abilities than those in LV-NC group (P<0. 01). The protein expression of N-cadherin decreased and that of E-cadherin increased after STXBP4 expression was knocked down, while STXBP4 overexpression exerted the opposite effects (P<0. 05). (3)In vivo, overexpression of STXBP4 increased the volume and weight of xenograft tumors in nude mice (P<0. 05). CONCLUSION: High expression of STXBP4 promotes the proliferation and migration of OSCC cells, and its effect on the migration behavior of OSCC cells may be related to EMT. [ABSTRACT FROM AUTHOR]