This study aimed to introduce a new method based on Hollow Fiber in order to determination of acetic anhydride (AA) in the air. Hydroxylamine hydrochloride and sodium hydroxide (1:1), were used as extraction solvent. This method was studied in the laboratory under various conditions. In order to make different concentrations of AA in the air, a standard glass chamber was used. The optimization of the sampling parameters and breakthrough volume was performed using the response surface method (RSM) and Design-Expert software (v.11.0). The results of the study indicated that the optimum sampling rate was 10 mL/min. The repeatability estimates of the proposed method including intra and inter-day were in the confine of 0.079–0.11 and 0.081–0.14, respectively. The limit of detection (LOD) and limit of quantitation (LOQ) of the examined analytes were 0.003 and 0.009 ng/mL, respectively. The storage time for the HF sampling method was seven days at laboratory temperature. The overall conclusion is that the HF sampling method showed a great sensitivity for the sampling of AA in the air. It could be assumed that HF sampling method is a fast, reliable and sensitive method and had a proper performance in the sampling of AA, compared to the National Institute for Occupational Safety and Health (NIOSH)- 3506 method.