The invention discloses a pipeline leakage location calculation method based on pressure difference. The calculation method comprises the following steps: establishing a pipeline leakage model; calculating an equation of negative pressure wave edge pipe attenuation; and finally, deducing the relationship between the pipeline leakage position and the pressure changes before and after pipeline leakage. In a simulation experiment, a negative pressure wave time-domain curve model is established for the first time according to fluid dynamics, the model is capable of simulating an actual pipeline, and dividing the negative pressure wave into three parts, namely respectively a steady state before leakage, an unsteady state during leakage and a steady state after leakage. An ANPW positioning algorithm and the traditional positioning algorithm can be compared by virtue of negative pressure wave simulated analysis, and the advantages of the ANPW positioning algorithm are obtained.