Abstract: To address the unclear motion response and unique single-point mooring characteristics of hybrid-structure aquaculture vessels under moored conditions, this paper takes the "Dehai No. 1" hybrid-structure aquaculture vessel (Bow and stern panel frame structures, middle truss structure) as the research object, and adopts the panel method based on potential flow theory and the Morison equation to perform time-domain analysis and calculation of the aquaculture vessel in a moored state. We systematically analyzed the effects of the presence of netting, variations in draft depth, as well as changes in environmental water depth on the motion response and mooring forces, and explored the variation of mooring forces of the aquaculture vessel under different anchor chain parameters. The calculations were based on the self-survival condition using the 15-year return period typhoon parameters in the Wanshan sea area of the northern South China Sea (Water depth 20 m), and four typical environmental cases were set up on the basis of head waves at the bow, including the collinear wind-wave-current case (Case I) and the multi-directional combination cases (Cases II–IV). The results showed that the mooring force on the aquaculture vessel was the largest when wind, waves, and current were in the same direction. The mooring force of the aquaculture vessel with netting was 1.35 times that of the vessel without netting, and the minimum laid chain length of the vessel with netting was reduced by up to 23% compared with that without netting. The roll modal response was the smallest in Case I and the largest in Case IV, while the pitch modal response showed the opposite trend. The presence of netting increased roll and slightly reduced heave and pitch, and increasing draft suppressed heave and pitch, while the mooring force and minimum grounded chain length decreased with increasing water depth. The mooring force reached its maximum at a draft of 4 m, and decreased with increasing water depth. As the anchor chain length increased, the maximum mooring force exhibited a gradually decreasing trend. With increasing sinker block mass, the maximum mooring force first decreased and then increased. With increasing distance from the sinker block to the anchor point, the maximum mooring force first increased and then decreased, and the anchoring system achieved the optimal comprehensive performance at an anchor chain length of 100 m, a sinker block mass of 5 400 kg, and a distance of 40 m from the sinker block to the anchor point.