Physical simulation experiments were made to research on the stress sensitivity on physical property of low permeability reservoir rocks. The experimental results shown that effective pressure had good exponential relationship with reservoir permeability. Combining with materaial balance method, reservoir engineering and rational deducation was made to reserach on water-flooding timing of low permeability reservoir development. Several production targets were obtained by these method, such as formation pressure, water and oil production, water cut and so on. The results shown that advanced water-flooding was very important in low permeability reservoir development to reduce the bad impact of stress sensitivity on formation permeability and maintain formation pressure.