China is a country with shortage of fresh water resources, and the exploitation of brackish water is an important way which can mitigate the contradiction between water supply and demand in the north of China. The effects of the irrigation with fresh and brackish water on soil and the growth of cotton were studied under wheat straw mulching. The results showed that soil salt content could increase after irrigated and the growth of cotton was restrained to some extent when irrigated with brackish water. Wheat straw mulching can effectively decrease soil surface evaporation and conserve soil moisture. Moreover, wheat straw mulching can effectively restrain soil surface salification caused by irrigation with brackish water and mitigating the negative effect of irrigation with brackish water on the growth of cotton. Therefore, in dry seasons the brackish water resources with mineral concentration between 2～5 g/L can directly be used to irrigate cotton and soil salt content would not exceed the tolerance of salinity of cotton. Under wheat straw mulching, the negative effects of irrigation with brackish water on soil and cotton can be reduced obviously.