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='font-weight:700;'>TSPYL5) and their potential clinical applications in HCC. METHODS: The methylation levels of ACP1, BMP4 and TSPYL5 were analyzed in 188 HCC tissues, 163 matched adjacent non-tumor tissues, and 29 normal liver tissues using a method of methylation-sensitive restriction enzyme-based quantitative PCR, and their associations with clinicopathological features and prognosis were evaluated. RESULTS: Compared with adjacent non-tumor tissues and normal liver tissues, the methylation levels of ACP1, BMP4, and TSPYL5 were significantly increased in HCC tissues (All p < 0.0001). The methylation of each individual gene could distinguish HCC tissues well from adjacent non-tumor tissues with the area under the receiver operating characteristic curves (AUC) of 0.753, 0.785 and 0.917, respectively. Furthermore, a higher methylation of BMP4 was statistically associated with worse disease-free survival (p = 0.006) and might be an independent unfavorable factor for disease-free survival by univariate and multivariate analysis (p = 0.011, HR 3.431, 95 % CI 1.333-8.833). CONCLUSIONS: Our findings suggest that hypermethylation of ACP1, BMP4, and TSPYL5 are common events in HCC and could be used as potentially detectable biomarkers in HCC tissues. Moreover, BMP4 could be potentially served as a methylated biomarker to predict recurrence and metastasis after hepatectomy for HCC patients. However, their potential clinical application value need to be further clarified.