The drip irrigation under mulch has become one of significant supporting technologies for cotton industry development in Xinjiang, and has shown the good economic and ecological benefits. With the rapid development of society and economy in Southern Xinjiang, the conventional mode of large-quota winter and spring irrigation, salt leaching and alkali decreasing is difficult to support sustainable development of land and water resources in Southern Xinjiang. This study tries to adjust soil moisture and salt content regulation mode of massive water salt leaching and drip irrigation under mulch in the non-growing period of cotton field in Southern Xinjiang, explores interannual soil salinity change features of drip irrigation cotton field without winter and spring irrigation, and provides experimental basis for drip irrigation technology under mulch which can reduce and exempt cotton irrigation in winter and spring. According to ET0, the dual-factor complete combination experiment involving 3 irrigating water quotas (I1, I2, I3) and 2 irrigation times (T12, T16) was designed, and 6 treatments were involved in total(I1T12,I2T12,I3T12,I1T16,I2T16 and I3T16). The investigation results of four-year (2012–2015) field positioning experiment showed that, under the condition of “germination under drip irrigation” without winter and spring irrigation, increasing irrigation quota and irrigation times could lower 0-100cm soil salinity accumulation, but the soil salinity accumulation degree was 40-100cm, and less than 0-30cm. In the seedling stage, bud stage, blossom and boll-forming stage, and boll opening stage, the average salinity of 0-100cm soil increased by 39.81%, 31.91%, 26.85% and 29.47%, respectively. Increasing irrigation quota and irrigation times could ease interannual soil salinity accumulation degree of cotton field with drip irrigation under mulch, without winter and spring irrigation. 0-100cm soil salinity before sowing was related to the irrigation quota of cotton in the growing stage of the last year. The larger the irrigation quota was, the smaller the soil salinity before sowing would be. The accumulation amount of soil salinity at the end of growing stage under different treatments was lower than that before sowing. The drip irrigation of cotton under mulch in the growing stage could effectively regulate soil salinity distribution and space-time migration process in the growing stage of cotton. Compared with the beginning of 2012, 0-100cm average soil salinity under 3 irrigation quotas (I1, I2, I3) was 33.66%, 5.60% and 1.24%, respectively. Salt accumulating rates under 12 irrigations and 16 irrigations were 20.66% and 6.33%, respectively. The soil had the risk of salinization when the “germination under drip irrigation” without winter and spring irrigation was used. Such results can provide the reference for prevention and treatment of soil moisture and salt content of cotton field with drip irrigation under mulch in the arid region.