Abstract: At present, most of the polymer thickeners used in water-based fracturing fluid both in China and abroad have poor salt resistance. Therefore, amphoteric polyacrylamide (AMPAM) was synthesized by introducing anionic monomer (2-acrylamido-2-methylpropane sulfonic acid (AMPS)) and cationic monomer (methacryloyloxyethyl trimethyl ammonium chloride (DMC)) into the acrylamide (AM) chain. The effects of the total mass fraction of monomers, mass ratio of monomers, initiator dosage, and pH value on the relative molecular mass and thickening property of AMPAM were studied, and the optimal conditions for AMPAM synthesis were determined. In addition, the salt resistance, solubility, and thickening property of AMPAM, as well as the performance of AMPAM fracturing fluid prepared with NaCl solution with salinity of 30 g/L were evaluated. The results show that the apparent viscosity of AMPAM solution of 0.5% prepared with high-salinity brine was 20 mPa·s, and the AMPAM was completely dissolved within 20 min when its dosage did not exceed 0.6%. The temperature and shear resistance, as well as sand-carrying and gel-breaking properties of AMPAM fracturing fluid prepared with brine meet the general technical requirements of water-based fracturing fluid. The results show that AMPAM has excellent salt resistance and can be used as a thickener for brine polymer fracturing fluid.