High-Mobility Group (HMG) is a group of DNA-binding proteins that are involved in a wide range of gene regulation processes such as transcription, replication, and DNA repair. Although the HMG proteins can be classified into sub-groups according to their DNA sequence specificity, a common feature of both groups is that they bind to the minor groove of DNA and induce the bending of DNA to different extents. However, even the diffusion mechanisms of the HMG proteins remain mostly unknown. Here we used molecular dynamics simulations to study the binding and sliding of a sequence-nonspecific HMG protein Nhp6A and a sequence-specific HMG protein Sox2 on DNA. Our results provided evidence for the two-mode diffusion of Nhp6A, which is consistent with the single-molecule experiments. For Sox2, our simulations presented a possible connection of its ability to induce DNA bending to its biological function of gene regulation.