Low oil production and rapid production decline epitomize the challenges of unconventional reservoir development. Rocks in the formation with micro-/nanoscale pore-throat units possess an immense surface area. Consequently, the wettability of rocks plays a crucial role in the relative permeability of oil/water, the injection pressure, the distribution and morphology of residual oil, and hence the ultimate oil recovery. Contact angle, as a frequently used method to evaluate wettability, is susceptible to oil-water saturation, imbibition, and surface roughness of rock slices. In addition, the measurement scale (droplet of several millimeters) does not match the flow scale (pore units in micro-or nanoscale). Therefore, this paper established a new wettability evaluation method based on oil−rock interaction. Molecular dynamics simulation results demonstrated that the interaction energy between the oil molecule and walls with different wettabilities shows a distinct discrepancy. Accordingly, nanomechanics by AFM was utilized to measure the oil molecule−pore wall interaction force. It was found that the interaction force increases with the augmented hydrophobicity of the pore wall due to hydrophobic force. In addition, the reservoir rock wettability index was defined using the oil−rock interaction force in the nanoscale. The wettability index has an excellent linear correlation with the intrinsic contact angle. The wettability evaluation method based on the oil−rock interaction force is more direct, facile, and rapid and overcomes the limitation of the traditional contact angle method.