Abstract: ob＜x＞jective To explore the effect of microRNA-6852 (miR-6852) on the radiosensitivity of colon cancer cells and its possible mechanism. Methods Human normal colonic epithelial cells HCoEpiC and human colon cancer cells SW480 were cultured in vitro, and the cells were irradiated with X-ray radiation field. qRT-PCR and Western blot were used to detect the ex＜x＞pression of miR-6852, LEF1 and AKR1C3 in cells; The luciferase reporter gene experiment was used to detect the targeted binding of miR-6852 to LEF1, LEF1 and AKR1C3; EdU was used to detect cell proliferation; Cytometry was used to detect apoptosis; ChIP-PCR was used to detect the targeted binding of LEF1 to the AKR1C3 promoter region. Results Compared with the HCoEpiC group, the ex＜x＞pression of miR-6852 in the SW480 group was significantly reduced (P＜0.05), and the ex＜x＞pression of LEF1 mRNA and protein, and the ex＜x＞pression of AKR1C3 mRNA and protein were significantly increased (P＜0.05). Compared with the blank control group, the ex＜x＞pression of miR-6852 in SW480 cells in the 2Gy group, 4Gy group and 6Gy group was significantly reduced (P＜0.05), and the ex＜x＞pression of LEF1 mRNA and protein, and the ex＜x＞pression of AKR1C3 mRNA and protein were significantly increased (P＜0.05). miR-6852 targeted and regulated the ex＜x＞pression of LEF1. There was no significant difference between the blank control+6Gy group and the miR-NC+oe-NC+6Gy group (P>0.05); Compared with the miR-NC+oe-NC+6Gy group, the number of EdU positive cells in SW480 cells in miR-6852-mimic+oe-NC+6Gy group were significantly reduced (P<0.05), while the apoptosis rate was significantly increased (P< 0.05); Compared with the miR-6852-mimic+oe-NC+6Gy group, the number of EdU-positive cells in the miR-6852-mimic+oe-LEF1+6Gy group was significantly increased (P<0.05), while the apoptosis rate was significantly reduced (P <0.05). LEF1 up-regulated the ex＜x＞pression of AKR1C3 by targeting the AKR1C3 promoter region. There was no significant difference between the blank control+6Gy group and the oe-NC+sh-NC+6Gy group (P>0.05); Compared with the oe-NC+sh-NC+6Gy group, the number of EdU-positive cells in SW480 cells in the oe-LEF1+sh-NC+6Gy group was significantly increased (P＜0.05), and the apoptosis rate was significantly reduced (P＜0.05) ; Compared with the oe-LEF1+sh-NC+6Gy group, the number of EdU-positive cells in the oe-LEF1+sh-AKR1C3+6Gy group was significantly reduced (P<0.05), and the apoptosis rate was significantly increased (P<0.05). Conclusion MiR-6852 targets the LEF1/AKR1C3 axis to increase the sensitivity of colon cancer cells to radiotherapy.