To improve metallographic structures and lubricating properties of hot rolled strips, a multifunctional MoS2 nano-lubricant was proposed for hot rolling process. Through hot rolling tests and relevant characterization methods of energy dispersive spectrometer (EDS) and field-emission scanning electron microscopy (FESEM), the multifunctional MoS2 nano-lubricant was proved to have both improved metallographic structures and lubricating properties. Not only the rolling forces were decreased, the thickness of oxidized scale was also reduced from 30–35 μm to 16–18 μm by using the MoS2 nano-lubricant. The grains in metallographic structure were observed to be refined obviously, and the orientations of pearlite lamellae were more multidirectional. There were also some carbide precipitates with dispersion strengthening effect appeared around grain boundary. The presence of Mo atoms within the iron matrix indicates the improved metallographic structure as a result of the diffusion of MoS2 nanosheets. This behavior is further instigated using thermal diffusion test, hot compression test, and molecular dynamics (MD) simulation. The results show that the metallographic structure improving effect of multifunctional MoS2 nano-lubricant was attributed to the interaction between MoS2 nanosheets and strips under the high-temperature and high-pressure condition of hot rolling process. In the presence of such high pressure, Mo atoms in MoS2 nanosheets could diffuse through the oxidized scale and exist in the iron matrix. The interaction between Fe and MoS2 nanosheets, meanwhile, was stronger. The diffused Mo atoms in iron matrix could form some coordination complexes with Fe atoms, which promote the nucleation of cementite, and playing a role in grain refinement. Therefore, the bifurcation growth was significantly enhanced, thus the growth directions of pearlite were also increased significantly. The researches provided not only theoretical basis for the development of multifunctional nano-lubricant with integrated metallographic structure improving effect, but also a new path for surface strengthening of strips.