Abstract Catalytic ethanol steam reforming (ESR) offers a sustainable and attractive route for hydrogen production, which can be utilized as a substitute for fossil fuels. ESR for hydrogen production involves complex reactions and yield of hydrogen depends upon several process variables such as temperature, molar feed ratio and pressure. In this study, a thermodynamics analysis coupled with experimentation for ESR toward hydrogen production has been investigated. The structured montmorillonite (MMT) nanoclay and TiO2 supported catalyst incorporated by nickel (Ni) was developed via a sol-gel and impregnation methods. The catalyst samples were characterized by XRD, FE-SEM, EDX, BET and TGA to understand crystallinity, surface morphology, pore structure and stability. Initially, thermodynamic analysis was employed to study the effect of reaction conditions on equilibrium product distribution of ESR. The equilibrium concentrations of different compounds were calculated by the method of direct minimization of the Gibbs free energy. Optimum conditions for ESR were found to be; atmospheric pressure, temperatures between 600 and 700 °C and steam to ethanol (S/E) feed molar ratio of 10:1, at which highest hydrogen can be produced with minimum coke formation. Next, catalytic performance of NiO/MMT-TiO2 catalyst for enhanced ESR for hydrogen production was conducted in a tubular fixed bed reactor at 500 °C and atmospheric pressure. Noticeably, Ni-promoted TiO2 NPs found efficient for selective hydrogen production, yet MMT-supported Ni/TiO2 gave much higher ethanol conversion with improved hydrogen yield. Using 12% Ni-10% MMT/TiO2 catalyst, ethanol conversion of 89% with H2 selectivity and yield of 61 and 55%, respectively were obtained. The stability test revealed MMT-supported catalysts maintained activity even after 20 h. By comparing results, it was possible to explain deviations between thermodynamic analysis and experimental results regarding carbon deposition and selective hydrogen production.