Summary To solve the problem of poor salt resistance of conventional drag reducers, a hydrophobic associative polymer drag reducer was prepared by inverse emulsion polymerization with acrylamide (AM), methacrylic acid (MAA), 2-acrylamide-2-methylpropane sulfonic acid (AMPS), and hexadecyl dimethyl allyl ammonium chloride (C16DMAAC) as the main monomers. The synthetic product was confirmed as the target product by infrared (IR), nuclear magnetic resonance (NMR), and mass spectrometry (MS). The viscosity-average molecular weight of the prepared drag reducer is 1100×104 g/mol. The pipeline friction results show that the drag reducer has good friction reduction and salt resistance. When the concentration in clean water is 0.06%, the maximum friction reduction rate is 71.1%. When the salinity is 5×104 mg/L, the calcium ion concentration is 2000 mg/L, and the suspended solid content is 500 mg/L, the maximum friction reduction rate is 68.9% when the concentration of the drag reducer is 0.06%. Salt water will not significantly lower the friction reduction rate. If the concentration of the drag reducer is increased to 0.08%, the maximum drag reduction rate will reach 73.8%. The microrheological test results of the friction reducer solution show that, at 0.2% concentration, there is no network structure between friction reducer molecules, which is consistent with Newtonian fluids possessing a certain viscosity. The elasticity index (EI) of the drag reducer solution is basically unchanged over time, maintaining good friction reduction and sand-carrying performance during the shearing process of large displacement pumping.