Abstract Natural gas steam reforming is commonly used for hydrogen production. However, research has shown that ethanol autothermal reforming can produce cleaner hydrogen gas efficiently. Despite this, there is a lack of studies on the energy self-sufficiency conditions of the ethanol autothermal reform. In this paper, we use simulations and the Response Surface Methodology (RSM) for the multivariate analysis of the energy self-sufficiency conditions in this process. First, we constructed and validated an industrial flowchart. After that, RSM allowed us to assess the process variables effects. The process variables studied were temperature (0 to 1000 ºC), pressure (20 to 30 bar), steam/ethanol ratio (2 to 5 mol/mol) and O2/ethanol ratio (0 to 1.5 mol/mol). We observe that the temperature and steam/ethanol ratio increase have a positive effect on hydrogen production. On the contrary, the O2/ethanol ratio increase has a negative effect, and the pressure increase is not statistically significant on hydrogen production. Therefore, the pressure was used at its minimum level (20 bar) while the temperature and the steam/ethanol ratio at its maximum levels (1000 ºC and 5 mol/mol). We also evaluated the energy consumption for the Autothermal Reactor (ATR). The reactor consumed 477.92 kJ/mol ethanol to produce 5.12 mol H2/mol ethanol when we use 1000 ºC, 20 bar, steam/ethanol 5 mol/mol, and O2/ethanol 0 mol/mol. ATR's energy self-sufficiency is achieved by using 1000 ºC, 20 bar, steam/ethanol 5 mol/mol, and O2/ethanol 0.86 mol/mol. In these conditions, 3.95 mol H2/mol ethanol is produced with 0 kJ/mol ethanol.