Saline-alkali land is a potentially exploitable reserve cultivated land resource, but it severely restricted the sustainable development of agricultural production. Owing to some factors such as the decreasing degree of cotton mechanization, increasing input of labor cost and production goods, declining comparative benefits, and implementing the strategy of food security, the cotton area in the Yangtze River and Yellow River is declining sharply, and the planting area is transferred to Binhai saline-alkali lands. Since the study of ecological security of planting Bt cotton in saline-alkali land is rare, it became the focus of many research studies worldwide. Whether the resistance of transgenic Bt cotton to cotton bollworm has been affected remains to be elucidated. Resistance is directly related to the environment safety of transgenic Bt cotton; therefore, there is an urgent need to solve the problems in cotton production. With the non-transgenic cotton as the control, we measured the corrected mortality of transgenic Bt cotton to cotton bollworm larvae and the contents of exogenous protein of transgenic Bt cotton that was planted in the low-, medium-and high-salt soil at seedling, budding, and flowering and bolling stages, respectively. The results showed that at the seedling, budding, and flowering and bolling stages of transgenic Bt cotton in low salt stress, the correction mortality of transgenic Bt cotton planted in the medium-and high-salt soil to cotton bollworm larvae decreased by 9.22%-47.46%, 31.61%-45.42%, and 3.59%-18.52%, respectively. Over the same period of Bt cotton, soil salinity significantly inhibited the expression of Bt protein in cotton leaves and decreased by 7.66%-29.86%, 3.77%-36.85%, and 18.13%-41.02% at seedling, budding, and flowering and bolling stages, respectively. There is a significant positive correlation between the efficiency of insect resistance of transgenic Bt cotton to cotton bollworm larvae and Bt protein content. Therefore, soil salinity levels inhibited the exogenous protein expression of transgenic Bt cotton, which led to the decreased resistance of transgenic Bt cotton on cotton bollworm. The present study on the effects and mechanisms of soil salinity on the influence of transgenic Bt cotton to cotton bollworm can provide a comprehensive basis for establishing Bt cotton pest prevention and control technology system, environmental safety evaluation, and safety management in soil salinity in Bt cotton fields.