BACKGROUND Many authors stated that cavities or air-gaps were the main challenge of dose calculation for head and neck with flattening filter medical linear accelerator (Linac) irradiation. OBJECTIVE The study aimed to evaluate the effect of air-gap dose calculation on flattening-filter-free (FFF) small field irradiation. METHODS In this comparative study, we did the experimental and Monte Carlo (MC) simulation to evaluate the presence of heterogeneities in radiotherapy. We simulated the dose distribution on virtual phantom and the patient's CT image to determine the air-gap effect of open small field and modulated photon beam, respectively. The dose ratio of air-gaps to tissue-equivalent was calculated both in Analytical Anisotropic Algorithm (AAA) and MC. RESULTS We found that the dose ratio of air to tissue-equivalent tends to decrease with a larger field size. This correlation was linear with a slope of -0.198±0.001 and -0.161±0.014 for both AAA and MC, respectively. On the other hand, the dose ratio below the air-gap was field size-dependent. The AAA to MC dose calculation as the impact of air-gap thickness and field size varied from 1.57% to 5.35% after the gap. Besides, patient's skin and oral cavity on head and neck case received a large dose discrepancy according to this study. CONCLUSIONS The dose air to tissue-equivalent ratio decreased with smaller air gaps and larger field sizes. Dose correction for AAA calculation of open small field size should be considered after small air-gaps. However, delivered beam from others gantry angle reduced this effect on clinical case.