The invention provides a method for determining lowering of fluid seepage resistance based on a nanotechnology. The method comprises the steps that first, according to different injection fluids and injection times of an actual working area, the injection process is divided into three stages, namely, the initial injection stage, the nano-solution injection stage and the replacement liquid injection stage; second, according to the seepage Darcy law and the injection times, the total cumulative injection amount of the fluids in a reservoir under the condition of the different injection times ineach of the three phases is determined; third, according to the linear relation between the total cumulative injection amount of the fluids and the injection pressure time integral, the slope of injection resistance curves of the three stages is determined; fourth, the resistance coefficient of the fluid in the reservoir in the nano-solution injection stage and the residual resistance coefficientof the fluid in the reservoir in the replacement liquid injection stage are determined correspondingly; and fifth, according to the relative magnitude relation of the two resistance coefficients in the fourth step, the effects of resistance lowering and injection increasing of the nanotechnology are evaluated. The determining method is accurate, reliable and high in practicability.