Abstract: In view of the poor performance of slick water at high salinity and high hardness condition, molecular weight and structure of resistance reducing agent has been analyzed. It is found that high molecular weight, linear molecular chain structure and functional monomers with large space hindrance of molecular side chain are beneficial to improve the resistance reducing ratio and salt tolerance. A kind of resistance reducing agent with high salinity resistance and high hardness resistance is developed, then the drainage agent and bactericides are added to form high salinity resistance and high hardness resistance slick water. The resistance reduction rate is up to 73% at 10×10⁴ mg/L mineralization degree and 3000 mg/L hardness. The field test has been carried out at 40 000 mg/L mineralization degree and 1000 mg/L hardness, estimated resistance reduction rate is up to 75%, and the construction curve is stable which shows good performance of reducing resistance.