Objective To study the pancreatic excitation peptide enzyme (pancreatic kallikrein, PK) in the clinical application of tacrolimus (tacrolimus, TAC) on the renal tubular epithelial cells induced by protective effect and its mechanism. Methods HK-2 cells were divided into pK (6 pg/mL) group, TAC (50 UG/mL) group, control group (CON group), TAC (50 UG/mL)+pK (6 pg/mL) group. CCK 8 was used to detect the condition of cells in each group and to determine the cell viability; The activity and quantity of reactive oxygen species (ROS) in cells were detected by the combination of dichlorodihydrofluorescein diacetate (DCFH DA) fluorescence and flow cytometry. The levels of bcl-2, Bax, lc3b and Beclin were detected by Western blot. Results The cell viability of PK group was significantly lower than that of con group, and the cell viability of TAC+PK group was significantly higher than that of TAC group (P＜0.05). The expression of ROS in TAC group was significantly higher than that in con group. Compared with TAC group, the expression of ROS in TAC+PK group was slightly lower (P＜0.05). The autophagy function of TAC group was higher than that of con group, and the expression of lc3b-Ⅱ and Beclin was stronger. The expression of lc3b-Ⅱ and Beclin in TAC+PK group was lower than that in TAC group (P＜0.05). The number of cell death in TAC group was greater than that in con group, and the ratio of bcl-2/Bax decreased. The ratio of bcl-2/Bax in TAC+PK group was significantly higher than that in TAC group (P＜0.05). Conclusion Pancreatic Kallidinogenase has a protective effect on renal tubular epithelial cells induced by tacrolimus. Its mechanism is related to the inhibition of antioxidant stress and the regulation of autophagy by Pancreatic Kallidinogenase.