To solve the problem that traditional image registration methods based on continuous optimization for large motion lung 4D CT image sequences are easy to fall into local optimal solutions and lead to serious misregistration, a novel image registration method based on high-order Markov Random Field (MRF) is proposed. By analyzing the effect of the deformation field constraint of the potential functions with different order cliques in MRF model, energy functions with high-order cliques form are designed separately for 2D and 3D images to preserve topology of the deformation field. In order to preserve the topology of the deformation field more effectively, it is necessary to apply a smooth term and a topology preservation term simultaneously in the energy function and use logarithmic function to impose a penalty on the Jacobian matrix with high-order cliques in the topology preservation term. For the complexity of the designed energy function with high-order cliques form, Markov Chain Monte Carlo (MCMC) algorithm is used to solve the optimization problem of the designed energy function. To address the high computational requirements in lung 4D CT image registration, a multi-level processing strategy is adopted to reduce the space complexity of the proposed registration method and promotes the computational efficiency. In the DIR-lab dataset with 4D CT images and the COPD (Chronic Obstructive Pulmonary Disease) dataset with 3D CT images, the average target registration error (TRE) of our proposed method can reach 0.95 mm respectively.