Objective To explore the inhibitory effect and its mechanism of CS055[a selective histone deacetylase inhibitor(HDACi)]on human colon carcinoma in nude mice. Methods The xenograft model was established successfully.Fifty-five mice were divided into five groups and eleven blocks by randomized complete-block design.The mice were respectively gavaged by CS055 10. 0 mg/(kg·d)in the first group,5 mg/ (kg·d)in the second group and 2. 5 mg/(kg·d)in the third group, while the mice in fourth group were treated by intraperitoneal injection of 5-fluorouracil in a dose of 25. 0 mg/(kg·d)and those in the fifth group were gavaged by negative-control-drug 0. 1 ml/(10 g·d)as negative control group.After treatment, all nude mice were killed,and all the subcutaneous transplanted tumors were stripped and measured by calipers and scales.Inhibitory rate of tumor weight and tumor volume was calculated.Tissue hematoxylin and eosin (HE)staining and transmission electron microscopy detection were used to detect the tumor cell apoptosis. Western blotting was used to detect the expression of histone deacetylase 1(HDAC1), HDAC2, acetylated histone-H3(ac-H3), p21, cyclin dependent kinase 4(CDK4), and cysteinyl aspartate-specific protease (Caspase)-3. Results Compared to negative control group, the respective inhibition rate of tumor weight in high-dose group, mediate-dose group, low-dose group, and 5-fluorouracil group was 15. 36%(P> 0. 05),40. 27%(P 0. 05)and 55. 63%(P 0. 05), 40. 47%(P 0. 05) and 55. 74%(P<0. 01)respectively.CS055 could significantly inhibit the expression of HDAC1 and HDAC2,upregulate the level of acetylation of histone H3 and the expression of p21,Caspase-3, while downregulate the expression of CDK4 protein. Conclusion CS055 can inhibit the growth of human colon carcinoma xenograft tumor probably by inhibiting the expression of HDAC1 and HDAC2, upregulating the level of histone H3 acetylation and the expression of p21 protein, downregulating the expression of CDK4 protein, which promotes tumor cell cycle arrest, and upregulating the expression of Caspase-3 protein, which induces LoVo cells apoptosis. Key words: Colorectal cancer; Histone deacetylase inhibitor; Apoptosis; Nude mice