In this study, the Sargassum angustifolium macroalgae was used as the feedstock of the hydrothermal liquefaction (HTL) process. The effects of operating conditions of temperature, residence time, and feedstock concentration on the yield of the HTL products were modeled using the response surface methodology of the Box-Benken design. Based on the proposed model, the maximum biocrude yield was predicted at 350°C, 35 min residence time, and 8.6 wt% of the feedstock concentration, confirmed by the experiment. The biocrude has a higher heating value of 33.91 MJ/kg, with the main components including ketones and alkanes. Sensitivity analysis of operating conditions revealed that the HTL process temperature has the most effect on the yield of products, and increasing temperature causes an increase in the biocrude and gas phase yields while decreasing the aqueous and solid phase yields. Among the cross-effect of parameters, the temperature-residence time interaction has the highest impact on the biocrude and gas phase yields. A comparison of the structural analysis of the solid phase and the algae showed the solid residue of the HTL process is highly porous and potentially a good candidate as an adsorbent. The physicochemical properties of the aqueous phase revealed its potential application to algae cultivation. Finally, three pretreatment methods of ultrasonication, microwave irradiation, and size variation of the feedstock were used to increase the biocrude yield at both maximum and minimum yield conditions. The results showed that microwave-assisted HTL is the most effective process, increasing the biocrude yield from 26.15 wt% to 34.77 wt%.