〔Abstract〕 Objective To investigate the expression of synaptotagmin 1 (SYT1) in hepatocellular carcinoma (HCC) and its clinical value. Methods Bioinformatics analysis was performed to predict the subcellular localization and expression of SYT1 in the tumor microenvironment (TME),as well as its biological functions in the progression of HCC. The expression of SYT1 in HCC tissues was verified by UALCAN, TIMER3.0 and HPA databases combined with IHC, and its correlation with MKI67 was analyzed. Combined with GEPIA2, TIMER3.0 databases and Rlanguage, the association of SYT1 expression level with the prognosis of HCC patients was explored, and survival analysis was carried out. Lentivirus-mediated SYT1 gene silencing was conducted, and the effects of SYT1 on the biological behaviors of HCC cells were explored by colony formation assay, EdU staining assay, cell scratch assay, and Transwell assay. The tumor-promoting effect of SYT1 was further validated in a nude mouse xenograft model. Results Bioinformatics prediction indicated that SYT1 is localized to the cell membrane and cytoplasm,and the expression of its family genes is mainly positively correlated. In HCC tissues, SYT1 expression was significantly upregulated (P=2.93×10-10) and positively correlated with MKI67 (ρs=0.419, P=3.3×10-17). Survival analysis showed that high SYT1 expression predicted poorer overall survival (P=0.015) and disease-specific survival (P=0.046 2) in HCC. Immune profiling analysis demonstrated that SYT1 was highly expressed in monocytes/macrophages, B cells and malignant cells in the TME. Enrichment analysis indicated that SYT1 may participate in multiple signaling pathways associated with HCC progression (P<0.05). IHC confirmed that the staining intensity of SYT1 was elevated in HCC tissues (P<0.000 1). Cellular assays showed that silencing SYT1 suppressed the proliferation, migration, and invasion of HCC cells (P<0.01). Animal experiments demonstrated that knockdown of SYT1 inhibited tumor growth in vivo (P<0.001).Conclusion SYT1 is upregulated in HCC and closely correlated with poor prognosis. It can promote the proliferation, migration and invasion of HCC cells as well as in vivo tumor growth, and is expected to become a potential novel target for the clinical treatment of HCC.