Aiming at the problem of high injection pressure caused by particle migration and the blocking of reservoir pore throat in the water injection process of loose low permeability sandstone reservoir with high content clay，a neutral gradient anti-plugging system was optimized through laboratory experiments. The lower speed gradient anti-plugging system consisted of 0.5% KCl clay stabilizer，and the higher speed gradient anti-plugging system consisted of 0.2% KCl and 0.3% organic cationic clay stabilizer （YN）. The anti-swelling performance of the gradient anti-plugging system and the changes of core pressure and permeability during displacement were investigated. The results showed that the anti-swelling rate of the system was about 91%. Compared with blank produced water（0.75 mL/min）displacement，at a lower speed（0.25 mL/min），the pressure growth multiple was reduced from 5.41 to 2.03 after 0.5% KCl displacement，and the permeability retention rate was increased from 18.49% to 49.15%. At higher speed（0.50 mL/min），the core permeability was gradually restored after displacement by 0.2% KCl and 0.3% YN system. After produced water displacement of 8 PV by 0.75 mL/min，the permeability retention rate was increased from 10.56% to 91.58%，and the pressure growth multiple was reduced from 9.47 to 3.28. Through the synergistic effect of velocity gradient and plugging prevention system，obvious plugging prevention and pressure reduction effect was obtained.