In view of characteristics of large time delay, multi-interference and strong coupling in temperature and humidity control system, an adaptive decoupling strategy based on generalized predictive control (GPC) and multi-model control is proposed in this paper. The proposed strategy mainly contains muti-model control, GPC decoupling control and adaptive algorithm. In multi-model control, multi-model sets are established to prevent the model mismatch in different working conditions. Meanwhile, this paper designs adaptive dynamic decoupling algorithms based on the principle of GPC. In actual experiments, temperature and humidity achieve precision of ±0.2°C and ±0.5% respectively.