Purpose: Previous studies have shown a correlation between the expression of H3K27me3 and pathological characteristics of malignant tumors. This study aimed to investigate the association of H3K27me3 and VEGF expression with clinical outcomes of synovial sarcoma patients. Methods: This study included 48 patients with synovial sarcoma. H3K27me3 and VEGF levels were evaluated by immunohistochemical staining, and their correlation with clinical parameters was analyzed by Spearman's and Pearson's test. Univariate and multivariate Cox regression analyses were used to identify potential prognostic factors. Kaplan-Meier method was used to analyze overall survival. Results: Protein levels of both H3K27me3 and VEGF were significantly associated with histologic grade (P = 0.004, P = 0.042, respectively), metastasis (P = 0.009, P = 0.028, respectively), and AJCC staging (P < 0.001, P = 0.003, respectively). H3K27me3 and VEGF expression showed positive correlation (P < 0.001, R = 0.618). Both H3K27me3 and VEGF expression were significantly associated with shorter overall survival by univariate analysis, but the association was significant for H3K27me3 [P = 0.26, HR = 2.640 (1.124-6.200)] only by multivariate analysis. Conclusions: H3K27me3 and VEGF expression are both significantly associated with overall survival of synovial sarcoma, and H3K27me3 is a significant independent prognostic indicator in patients with synovial sarcoma.