Selective etching of silicon oxide (SiO2) against silicon (Si) using anhydrous hydrogen fluoride (HF) vapor has been used for semiconductor device fabrication. We studied the underlying mechanism of the selective etching by density functional theory (DFT) calculation. We constructed surface slab models of SiO2 or Si with different degrees of fluorination and simulated the four steps of fluorination. The calculations show relatively low activation energies of 0.72–0.79 for the four steps of fluorination of SiO2, which are close to ∼0.69 observed in the experiment. The four-membered ring structure of –Si–O–H–F– in all transition states stabilized the system, resulting in relatively low activation energies.