The gray relational grade and stepwise regression analysis were conducted to analyze the relationship between seed cotton yield and major climate factors, including accumulated temperature, rainfall and sunshine hours, in cotton-wheat double cropping system in Huanghuaihai cotton region from 1993 to 2010. The results indicated that the yield variations among different years were mainly influenced by accumulated temperature above 20℃, and followed by sunshine hours and rainfall from April to October, with the correlation coefficients of 0.4463, 0.4052 and 0.3133, respectively. During the growing season,the yield was mainly affected by sunshine hours in August, sunshine hours in September and accumulated temperature above 20℃ in August. The correlation coefficients were 0.7201, 0.7116 and 0.7042, respectively. The stepwise regression analysis also showed that the accumulated temperature was the key factor positively affected the yield. In contrast, rainfall showed a negative effect. The regressive equation (P=0.0007598,R²=0.7477)can be applied to predict the seed cotton yield of cotton-wheat double cropping system in Huanghuaihai cotton region.