Silica solubility and molecular speciation in hydrothermal water vapor have been determined through quartz solubility experiments at 400–800 °C and 50–270 bar using a novel U-tube flow-through reactor system and theoretical calculations. The results demonstrate that silica concentrations are low in water vapor (mSi,tot = 0.11–4.56 mmol/kg or xSi,tot = 8.21 × 10−5–1.98 × 10−6 mol/mol) increase with both temperature and pressure, which is attributed to the dissolution of quartz according to the reaction:SiO2(s) + (n + 2)H2O(g) ⇋ Si(OH)4·(H2O)n(g)Thermodynamic modeling and theoretical calculations employing density functional theory (B3LYP-D3), and MP2 ab initio calculations reveal the stable structures to be Si(OH)4(g), Si(OH)4·(H2O)2(g), Si(OH)4·(H2O)4(g) and Si(OH)4·(H2O)7(g) (n = 0, 2, 4, 7) under the temperature and pressure conditions of interest, with higher-order hydrated structures also present at the lowest temperatures and highest pressures. Various isomers of the gaseous silica species were identified, with the number of energetically favorable structures increasing with hydration level and the motifs shifting from silanol-water bonds to complex water-water networks. Over the temperature range of interest, the logarithm of the quartz equilibrium solubility constant (logKn) rises from −7.40 to −6.55 and −12.23 to −11.65 at 400 to 800 °C for the formation of Si(OH)4(g) and Si(OH)4·(H2O)2(g), respectively, and decreases from −16.20 to −19.15 and –22.61 to −28.74 for Si(OH)4·(H2O)4(g) and Si(OH)4·(H2O)7(g) at the same temperature range, respectively. Standard thermodynamic properties were derived based on the experimental results, revealing temperature-independent enthalpy (ΔHn,ro), entropy (ΔSn,ro) and heat capacity (ΔCp,n,ro) of reaction for each gaseous silica species. The enthalpy of the reaction is nearly constant, whereas the entropy and heat capacity decrease with increasing hydration, resulting in higher-level hydrated species becoming less important with increasing temperature. Our quartz solubility results are in good agreement with previous experimental data and thermodynamic equations, as well as the thermodynamic properties of Si(OH)4(g) at 25 °C and 1 bar.