Water-based drilling fluids are characterized by cost-effective, wide sources of raw materials, and environmental friendliness. However, it is prone to cause various accidents that affect the drilling efficiency. One of the main problems is that conventional inhibitors cannot effectively suppress the hydration expansion of shale in Sichuan. In this study, we found that a mixture of Span 20 and Tween 60 can enhance the hydrophobicity of shale by forming a hydrophobic membrane on the shale surface, which reduces the number and weakens the hydrogen bond between water and shale, thereby greatly reducing the amount of water entering into the shale. Consequently, the hydration expansion rate of shale, dissolution of salts in the shale, and decrease of compressive strength are suppressed by adding the mixture of surfactants. Thereby, wellbore stability is maintained during drilling. The expansion rate of average hole diameter is only 7.47%, and the drilling rate was 1.71 times as fast as using oil-based mud in a nearby well in the field tests in Sichuan, China.