Hydrodeoxygenation (HDO) is considered as a substantial path for cleaner production of fatty acids and triglycerides into diesel range hydrocarbons (DRHs) (C15-C18) generally identified as green diesel fuel. Heterogeneous catalysis suggests a supplementary approach for the conversion of biomass into significant biochemicals possibly selective hydrocarbons by an inventive method. The present study reveals the optimization of reaction parameters for the process of HDO of rubber seed oil (RSO) over the transition metal NiMo/γ-Al2O3 (NMA) catalyst (designed via sonochemical co-impregnation approach) into DRHs, that is, n-C15-n-C18. The comprehensive studies have been performed to investigate the parametric effects employing response surface methodology using central composite design. The experimental design was conducted on the four most influential operating factors, namely, temperature within the range of 300-400 °C, weight hourly space velocity (WHSV) (1-3 h-1), H2/oil ratio (400-1000 N (cm3/cm3)), and pressure (30-80 bar), for triglyceride conversion and DRH yield. All the experimental runs were performed in continuous process using a fixed bed tubular reactor over the NMA catalyst. The product analysis showed that triglycerides are completely hydrodeoxygenated into DRHs with an optimum production of 84.94 wt yield led by prime reaction conditions at a temperature of 400 °C, WHSV of 1 h-1, pressure of 80 bar, and H2/oil ratio of 400 N (cm3/cm3). The parametric interaction between temperature and WHSV has significantly influenced the diesel yield. The investigations validated that HDO tracked the corresponding reaction condition in competitive mode and obligated the diverse optimum and limiting reaction conditions. In addition, deactivation of the catalyst study was performed at the optimized reaction condition. The catalyst was found to be active until 18 h without bringing to sulfidization process with 80 diesel yield and 100 triglyceride conversion. The slight deactivation of the catalyst is observed, with a very small amount coke deposition even after 18 h of time on stream at the optimized reaction condition. The novelty of the present study lies in the performance of sonochemically synthesized catalyst for HDO of RSO to produce green diesel and to optimize the reaction condition and catalysts deactivation performance at optimized reaction conditions. © 2020 American Chemical Society.