Objective: To further understand the methylation status, expression, function, and mechanism of RASSF10 in colorectal cancer.Method: Eight colorectal cancer cell lines, 89 cases of primary colorectal cancer, and 5 cases of normal colorectal mucosa were involved in this study.Methylation specific PCR, western blot, colony formation, siRNA, gene expression array, and xenograft mice were employed.Results: Loss of RASSF10 expression and complete methylation were found in LOVO, RKO, and HCT116 cells.Expression or reduced expression and partial methylation were found in LS180, DLD1, HT29, SW480, and SW620 cells.Restoration or increased expression of RASSF10 was found in these colorectal cancer cells by 5-aza-2-deoxycytidine treatment.RASSF10 was methylated in 60.7％ (54/89) of primary colorectal cancer samples.Methylation was associated with tumor stage (P ＜ 0.05) and metastasis (P ＜ 0.05).Re-expression of RASSF10 inhibited cell proliferation and induced apoptosis and G2/M phase arrest in RKO and HCT116 cells.HCT116 cells tumor xenograft was suppressed by RASSF10.Reduced expression of MDM2 was revealed by comparison of gene expression profile in RASSF10 expressed and unexpressed RKO cells.The result was confirmed by RT-PCR and western blot.RASSF10 activated P53 signaling in RKO and HCT116 cells after UV exposure.RASSF10 sensitized RKO and HCT116 cells to docetaxel.Conclusions: RASSF10 is frequently methylated in human colorectal cancer and the expression is regulated by promoter region hypermethylation.Methylation of RASSF10 is associated with late tumor stage and metastasis.RASSF10 suppresses human colorectal cancer growth by activating P53 signaling in colorectal cancer.RASSF10 sensitizes colorectal cancer to docetaxel.