Objective To find the key factors that have great influences on the bistable properties between let7 and LIN28 by exploring the effects of different parameters on the negative feedback bistable system, and provide insights for regulating the drug resistance generated during treatment. Methods The bistability of two-dimensional system was studied by dynamics modeling, and the influence of the parameters on stability behavior of the system was investigated from the portrait of nullclines. Results The parameters showed heterogeneous effects on bistability behavior of the system. A shift in parameter values could regulate the characteristics of bistability and might even make a switch back and forth between bistability and monostability. Conclusions Targeted regulation of sensitive parameters can potentially achieve the goal of controlling drug resistance.