In order to control the cascaded H-bridges (CHB) converter with staircase modulation strategy in a real-time manner, a real-time and closed-loop control algorithm based on artificial neural network (ANN) for three-phase CHB converter is proposed in this paper. It costs little computation time and memory. It has two steps. In the first step, hierarchical particle swarm optimizer with time-varying acceleration coefficient (HPSO-TVAC) algorithm is employed to minimize the total harmonic distortion (THD) and generate the optimal switching angles offline. In the second step, part of optimal switching angles are used to train an ANN and the well-designed ANN can generate optimal switching angles in a real-time manner. Compared with previous real-time algorithm, the proposed algorithm is suitable for a wider range of modulation index and results in a smaller THD and a lower calculation time. Furthermore, the well-designed ANN is embedded into a closed-loop control algorithm for CHB converter with variable direct voltage (DC) sources. Simulation results demonstrate that the proposed closed-loop control algorithm is able to quickly stabilize load voltage and minimize the line current's THD (<5%) when subjecting the DC sources disturbance or load disturbance. In real design stage, a switching angle pulse generation scheme is proposed and experiment results verify its correctness.