Rock compressive strength is an important mechanical parameter for the design, excavation, and stability analysis of rock mass engineering in cold regions. Accurate and rapid prediction of rock compressive strength has great engineering value in guiding the efficient construction of rock mass engineering in a cold regions. In this study, the prediction of triaxial compressive strength (TCS) for sandstone subjected to freeze-thaw cycles was proposed using a genetic algorithm (GA) and an artificial neural network (ANN). For this purpose, a database including four model inputs, namely, the longitudinal wave velocity, porosity, confining pressure, and number of freeze-thaw cycles, and one output, the TCS of the rock, was established. The structure, initial connection weights, and biases of the ANN were optimized progressively based on GA. After obtaining the optimal GA-ANN model, the performance of the GA-ANN model was compared with that of a simple ANN model. The results revealed that the proposed hybrid GA-ANN model had a higher accuracy in predicting the testing datasets than the simple ANN model: the root mean square error (RMSE), mean absolute error (MAE), and
R
squared (
R
2
) were equal to 1.083, 0.893, and 0.993, respectively, for the hybrid GA-ANN model, while the corresponding values were 2.676, 2.153, and 0.952 for the simple ANN model.