The invention relates to a multi-stage waterproof transformer substation with temperature and humidity regulation and control. The multi-stage waterproof transformer substation with temperature and humidity regulation and control comprises a box body, a supporting seat fixedly installed at the lower end of the box body, a waterproof system, a gap layer, a ventilation layer, a detection system and a control system, wherein the gap layer and the ventilation layer are arranged on the side face of the box body. The supporting seat isolates the box body from the ground. The waterproof system comprises a drainage top cover, a water level valve, a water storage tank, a water guide pipe and a spray head. A ventilation layer is arranged on the side wall of the box body and comprises a plurality of fans, exhaust holes and hole plugs. The detection system comprises a temperature detector A, a humidity detector A, a particle density detector A, a temperature detector B, a humidity detector B and a particle density detector B. According to the multi-stage waterproof transformer substation with the temperature and humidity regulation and control function, the control system controls the waterproof system and the ventilation layer according to the temperature, humidity and dust amount inside and outside the box body, effective water prevention is achieved, rainwater is collected to assist heat dissipation, a fan strengthens heat dissipation, and normal operation of the transformer substation is guaranteed.