Objective To optimize the fermentation process of pine pollen rice wine by Box-Behnken response surface design and entropy weight technique for order preference by similarity to an ideal solution (TOPSIS) method. Methods With pine pollen and glutinous rice as the main raw materials, sensory score, alcohol content and antioxidant capacity as evaluation indexes, a 3-factor and 3-level response surface test was designed based on the single factor test, and the addition of pine pollen, koji and fermentation time as investigation factors, according to the Box-Benhnken central combination test principle. The fermentation process of pine pollen rice wine was optimized by entropy weight TOPSIS method. Results The optimum fermentation process of pine pollen rice wine addition was 8%, koji addition 0.8% and fermentation time 72 h. Under these conditions, the texture of pine pollen rice wine was uniform, the taste was soft, and the color was light brown and yellow. After 3 batches of process verification experiments, the sensory score of rice wine was 89.5 points, the alcohol content was 17.2%vol, and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical clearance rate was 87.43%. Conclusion The method of entropy weight TOPSIS combined with response surface design to optimize the fermentation process of pine pollen rice wine is stable and predictable, which lays a theoretical foundation for the production of high quality pine pollen rice wine.