Aiming at predicting the purity of the extract and raffinate components in the simulated moving bed (SMB) chromatographic separation process, a soft-sensor modeling method was proposed by adoptig the hybrid learning algorithm based on an improved particle swarm optimization (PSO) algorithm and the least means squares (LMS) method to optimize the adaptive neural fuzzy inference system (ANFIS) parameters. The hybrid learning algorithm includes a premise parameter learning phase and a conclusion parameter learning phase. In the premise parameter learning stage, the input data space division of the SMB chromatographic separation process and the initialization of the premise parameters are realized based on the fuzzy C-means (FCM) clustering algorithm. Then, the improved PSO algorithm is used to calculate the excitation intensity and normalized excitation intensity of all the rules for each individual in the population. In the conclusion parameter learning phase, these linear parameters are identified by the LMS method. In order to improve population diversity and convergence accuracy, the population evolution rate function was defined. According to the relationship between population diversity, population fitness function and particle position change, a new adaptive population evolution particle swarm optimization (NAPEPSO) algorithm was proposed. The inertia weight is adaptively adjusted according to the evolution of the population and the change of the particle position, thereby improving the diversity of the particle swarm and the ability of the algorithm to jump out of the local optimal solution. The simulation results show that the proposed soft-sensor model can effectively predict the key economic and technical indicators of the SMB chromatographic separation process so as to meet the real-time and efficient operation of the SMB chromatographic separation process.