Objective To investigate the effects of X-ray dose on the expressions of microRNA-221 (miR-221) and phosphatase and a tensin homolog deleted from chromosome10 (PTEN) in human colorectal carcinoma (CRC) cells. Methods Human CRC-derived cell line, Caco2, was cultured conventionally. The cells were divided into five groups and exposed to different doses of X-ray (0, 2, 4, 6, and 8 Gy) respectively. The total RNA and protein of the Caco2 cells were extracted after irradiation, and the miR-221 and PTEN mRNA expressions were detected by real-time RT-PCR.Moreover, the protein alteration of PTEN in Caco2 cells was detected by Western-blot analysis. Results The radiation dose of X-ray significantly affected the expressions of miR-221 and PTEN protein in human Caco2 cells in a dose-depen-dent manner. Moreover, the miR-221 expression level was up-regulated gradually with the increase of irradiation dose, on the contrary, the PTEN protein expression level was down-regulated gradually (P<0.01). Conclusion The radiation dose can affect the miR-221 and PTEN protein expression pattern in CRC cells.