Bisphenol F (BPF) was synthesized from polyoxymethylene dimethyl ethers (PODEn, n=1～5) instead of formaldehyde (FA) of traditional process catalyzed by phosphorous acid (PA). Results showed that the yield of BPF was parabolic with the increase of n under the same temperature, that is, the yield firstly increased and then decreased. And the yield of BPF synthesis from PODE2 reached the maximum of 95.8%. The selectivity decreased with the increase of n. However, the selectivity of BPF synthesis from PODEn had obvious advantage compared with traditional synthesis technology from FA. By comprehensive consideration, PODE2 is the best starting material for substituting FA to synthesize BPF. Meanwhile, the effects of mole ratio of phenol (Ph) to PODE2, mole ratio of PA to PODE2, reaction temperature and reaction time on yield, selectivity and isomer distribution were also investigated. Based on single factor experiments, response surface methodology (RSM) was conducted to create a quadratic regression equation and obtain the optimal conditions of BPF synthesis from PODE2, which were mole ratio of Ph to PODE2 of 16.4, mole ratio of PA to PODE2 of 5.49 and reaction temperature of 90 ℃. At the optimum conditions, the yield reached 99.0% and the selectivity reached 95.8%.