Eco-friendly and low-cost water-based nanolubricants containing rutile TiO2 nanoparticles (NPs) were developed for accelerating their applications in industrial-scale hot steel rolling. The lubrication performance of developed nanolubricants was evaluated in a 2-high Hille 100 experimental rolling mill at a rolling temperature of 850◦ C in comparison to that of pure water. The results indicate that the use of nanolubricant enables one to decrease the rolling force, reduce the surface roughness and the oxide scale thickness, and enhance the surface hardness. In particular, the nanolubricant consisting of 4 wt % TiO2, 10 wt % glycerol, 0.2 wt % sodium dodecyl benzene sulfonate (SDBS) and 1 wt % Snailcool exhibits the best lubrication performance by lowering the rolling force, surface roughness and oxide scale thickness by up to 8.1%, 53.7% and 50%, respectively. The surface hardness is increased by 4.4%. The corresponding lubrication mechanisms are attributed to its superior wettability and thermal conductivity associated with the synergistic effect of rolling, mending and laminae forming that are contributed by TiO2 NPs.