In this study, the applications of different extractants in the separation of 1,1,1,3,3-pentafluoropropane/hydrogen fluoride mixtures at the molecular level (including the extraction mechanism) and on a systematic scale (including extraction performance analysis) were investigated. The optimal extractant was screened, and 99.9 % 1,1,1,3,3-pentafluoropropane and hydrogen fluoride was obtained by an extractive distillation process. The extractant screening results indicated that ethyl acetate was the most promising extractant for 1,1,1,3,3-pentafluoropropane, followed by dimethyl sulfoxide. Analysis of the relative volatility also validated that ethyl acetate can be used as an extractant for separating 1,1,1,3,3-pentafluoropropane/hydrogen fluoride mixtures. The extractive distillation process results showed the optimal C01 and C02 parameters as determined by the sequential iterative optimization method. Economic analysis indicated that the annual operating costs and equipment costs are $ 0.70 × 106 and $ 2.01 × 106, of which the equipment costs of C01 and C02 are 33.03 % and 23.91 %, respectively. Environmental analysis demonstrated that the amount and cost of CO2 emissions for extraction distillation using ethyl acetate are 1.22 × 104 t/y and 6.34 × 104 $/y, respectively, which are 71.36 % lower than those of pressure swing distillation process. In addition, a reduction in the operating time results in a significant reduction in the emission costs.