In order to solve the obvious nonlinear problem of temperature and complex structure of PCR instrument during nucleic acid amplification. In this paper, a new nucleic acid amplification device and temperature control algorithm were proposed. In the device, in order to improve the rise and fall rate and make the whole reaction device smaller and simpler, this paper uses a microfluidic chip for nucleic acid reaction. At the same time, in the warming and cooling module, the temperature is controlled by the semiconductor chilling plate, the air‐cooled cooling device and the heat sink structure, which greatly improves the speed of nucleic acid amplification. In the algorithm, a hybrid algorithm is designed, using Particle Swarm Optimization (PSO) to optimize PID algorithm parameters, and then based on fuzzy theory, according to the temperature control requirements of nucleic acid amplification, fuzzy rules are analyzed and fuzzy reasoning is carried out, and then combined with PID to achieve rapid response and overshooting control of temperature control. Finally, the measurement noise is filtered by Kalman filter. Finally, COMSOL and MATLAB software are used to simulate and compare, and it is proved that the device has a certain heat dissipation effect in the process of nucleic acid amplification. This algorithm can improve the accuracy and robustness of the control system, improve the response speed, reduce the overshoot, shorten the adjustment time, and restrain the interference.