Previous studies have indicated that women suffer from dry eye syndrome (DES) more significantly than men. Therefore, we specifically explore the associations between air pollutant levels and the risks of DES for women. The study obtained 27,605 participants from the 29 recruitment centers of the Taiwan Biobank, which was established in October 2012. A large scale cross-sectional study involving DES sufferers and age- and education-matched control groups without DES was designed. Based on the municipality of residence, the predicted concentration levels of various air pollutants, including PM2.5, sulfur dioxide (SO2), ozone (O3), and nitrogen dioxide (NO2) were estimated by using hybrid kriging/ LUR model. Multiple logistic regressions were applied to estimate the prevalence ratios (PR) of DES and 95% confidence interval. Hormone supplementations, DBP, allergies, and arthritis were considered as important comorbidities for increased PR risk of DES. In addition, with each standard deviation (SD) increment of PM2.5 and temperature, women had significant increases in PRs of DES of 1.09- and 1.07-fold, respectively; conversely, each SD increment of relative humidity (RH) had a protective effect against the risk of DES. After considering hormone supplementation, arthritis, and allergy, the SD increment of NO2 and temperature were associated with the PRs of DES. In conclusion, significant associations of ambient NO2 concentration, RH and temperature with DES indicated the importance of increased environmental protection in the female population. Female exposure to high levels of NO2 when receiving hormone supplementation, or suffering with allergies or arthritis, had significantly increased risk of DES.