To study the effects of phenylacetate ( PA ) on cell proliferation and homeobox (HOX) genes expression in the colorectal carcinoma HCT-8 cell line, HCT-8 cells were grown in the presence or absence of PA. The cellular proliferation inhibition was evaluated by the MTT assay. Twenty-two HOX genes were divided into three groups ( P1, P2,P3 ) according to their primer sequences, and the samples of cells were analyzed for the HOX genes mRNA expression by means of the semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The level of the HOX genes expression was expressed as the ratio expression rate of HOX gene to theβ-actin. HCT-8 cells were treated with 1.0-5.0 mmol/L PA for 24-72 h. With the increase of the PA concentration or the prolongation of the treating time, the cell proliferation is inhibited in a dose- and time-dependent manner. The P1 group mRNA * expression(0. 5781 ± 0. 0836) is significantly lower than that of the untreated group (0. 7701 ± 0. 0883 ) in HCT-8 cells (p＜0.001). Both the mRNA expressions of groups P2(0. 3941 ±0.0819) and P3(0.5601 ±0.0736) in the PA treated group are significantly higher than those of the untreated groups P2 (0. 1221 ± 0. 0782 ) and P3 (0. 1806 ±0. 0811 ) in HCT-8 cells (p ＜ 0. 001 ). PA could effectively inhibit cell proliferation by regulating the HOX genes expression and the mechanisms of the PA action are correlated with the transcription process in HCT-8 cells.