Non-edible Ceiba oil has the potential to be a sustainable biofuel resource in tropical countries that can replace a portion of today's fossil fuels. Catalytic deoxygenation of the Ceiba oil (high O/C ratio) was conducted to produce hydrocarbon biofuel (high H/C ratio) over NiO-CaO5/SiO2-Al2O3 catalyst with aims of high diesel selectivity and catalyst reusability. In the present study, response surface methodology (RSM) technique with Box-Behnken experimental designs (BBD) was used to evaluate and optimize liquid hydrocarbon yield by considering the following deoxygenation parameters: catalyst loading (1-9 wt. %), reaction temperature (300-380 °C) and reaction time (30-180 min). According to the RSM results, the maximum yield for liquid hydrocarbon n-(C8-C20) was found to be 77% at 340 °C within 105 min and 5 wt. % catalyst loading. In addition, the deoxygenation model showed that the catalyst loading-reaction time interaction has a major impact on the deoxygenation activity. Based on the product analysis, oxygenated species from Ceiba oil were successfully removed in the form of CO2/CO via decarboxylation/decarbonylation (deCOx) pathways. The NiO-CaO5/SiO2-Al2O3 catalyst rendered stable reusability for five consecutive runs with liquid hydrocarbon yield within the range of 66-75% with n-(C15 + C17) selectivity of 64-72%. Despite this, coke deposition was observed after several times of catalyst usage, which is due to the high deoxygenation temperature (> 300 °C) that resulted in unfavourable polymerization side reaction.