In order to improve the efficiency and accuracy of thermal and moisture comfort prediction of underwear, a new prediction model is designed by using principal component analysis method to reduce the dimension of related variables and eliminate the multi-collinearity relationship between variables, and then inputting the converted variables into genetic algorithm (GA) and BP neural network. In order to avoid the problems of slow convergence speed and easy falling into local minimum of Back Propagation (BP) neural network, this paper adopted GA to optimize the weights and thresholds of BP neural network, and utilized MATLAB software to program, and established the prediction models of BP neural network and GA–BP neural network. To verify the superiority of the model, the predicted result of GA–BP, PCA–BP and BP are compared with GA–BP neural network. The results show that PCA could improve the accuracy and adaptability of GA–BP neural network for thermal and moisture comfort prediction. PCA–GA–BP model is obviously superior to GA–BP, PCA–BP, BP, SVM and K-means prediction models, which could accurately predict thermal and moisture comfort of underwear. The model has better accuracy prediction and simpler structure.