Silica (SiO2) is an important mineral present in atmospheric mineral dust particles, and the heterogeneous reaction of N2O5 on atmospheric aerosol is one of the major pathways to remove nitrogen oxides from the atmosphere. The heterogeneous reaction of N2O5 with SiO2 has only been investigated by two studies previously, and the reported uptake coefficients differ by a factor of >10. In this work two complementary laboratory techniques were used to study the heterogeneous reaction of SiO2 particles with N2O5 at room temperature and at different relative humidities (RHs). The uptake coefficients of N2O5, γ(N2O5), were determined to be (7.2 ± 0.6) × 10–3 (1σ) at 7% RH and (5.3 ± 0.8) × 10–3 (1σ) at 40% RH for SiO2 particles, using the aerosol flow tube technique. We show that γ(N2O5) determined in this work can be reconciled with the two previous studies by accounting for the difference in geometric and BET derived aerosol surface areas. To probe the particle phase chemistry, individual micrometer sized SiO2 particles were optically levitated and exposed to a continuous flow of N2O5 at different RHs, and the composition of levitated particles was monitored online using Raman spectroscopy. This study represents the first investigation into the heterogeneous reactions of levitated individual SiO2 particles as a surrogate for mineral dust. Relative humidity was found to play a critical role: while no significant change of particle composition was observed by Raman spectroscopy during exposure to N2O5 at RH of <2%, increasing the RH led to the formation of nitrate species on the particle surface which could be completely removed after decreasing the RH back to <2%. This can be explained by the partitioning of HNO3 between the gas and adsorbed phases. The atmospheric implications of this work are discussed.