Currently, slip water fracturing fluid is widely used as a fracturing fluid for shale reservoirs. Non-ionic hydrophobic modified polyacrylamide (HM-PAM), partially hydrolyzed water-soluble hydrophobic associating polyacrylamide (HMWSP) and partially hydrolyzed anionic polyacrylamide (HPAM) solutions were modeled by molecular simulation software Materials Studio. The radius of gyration (Rg) and mean square displacement (MSD) of HPAM and HMWSP at different NaCl concentrations were calculated. From the simulation results, compared with HPAM and HM-PAM, HMWSP had a larger radius of gyration, a larger intrinsic viscosity number, and a larger hydrodynamic size, which would produce better drag reduction effects. Using acrylamide (AM), acrylic acid, 2-acrylamido-2-methylpropanesulfonic acid (AMPS) as basic raw materials, a hydrophobic associative drag reducer (HMWSP) was prepared by an inverse emulsion method. Infrared spectroscopy (FIIR) was used to characterize the synthesized products, and fluorescence chromatography was used to test the association of polymer solutions. Using a friction tester to test the drag reduction performance of the drag reducer, HMWSP has good resistance to salt reduction. HMWSP had good resistance reducing salt performance.