Objective To investigate the effect of Lycium barbarum polysaccharide and UCA1 siRNA individually, or in combination, on the proliferation and apoptosis of SH-SY5Y cells induced by MPP⁺ and its mechanism. Methods SH-SY5Y cells were treated with MPP⁺(0. 25, 0. 5, 1 and 2 mmol / L for 24 hours) and LBP (50, 100, 200 and 400 μg / mL Lycium barbarum polysaccharide pretreatment for 1 hour and then treated with MPP⁺ for 24 hours). The optimal concentrations of MPP⁺ ( 1 mmol / L) and LBP ( 400 μg / mL) were selected for subsequent experiments. The experiment was divided into four groups: control group ( without treatment ), MPP⁺ group ( cells were treated with 1 mmol / L MPP⁺ for 24 hours), Lycium barbarum polysaccharide group ( cells were pretreated with 400 μg / mL Lycium barbarum polysaccharide for 1 hour and then treated with 1 mmol / L MPP⁺ for 24 hours), si-UCA1 group ( cells were treated with 1 mmol / L MPP⁺ and then transfected with si-UCA1) and barbarum polysaccharide + si-UCA1 group. MTT assays were used to assess cell viability and flow cytometry was used to measure the apoptosis rate, ROS level and membrane potential. Results Compared with the control group, the cell survival rate and membrane potential in the MPP⁺ group were reduced significantly and the apoptosis rate and ROS level were increased significantly (P<0. 05). Compared with the MPP⁺ group, the cell survival rate and membrane potential in Lycium barbarum polysaccharide and si-UCA1 groups were increased significantly and the apoptosis rate and ROS level were decreased significantly (P<0. 05). Compared with Lycium barbarum polysaccharide and si-UCA1 groups, the cell survival rate and membrane potential in the LBP+si-UCA1 group were increased significantly and the apoptosis rate and ROS level were decreased significantly ( P< 0. 05 ). Conclusions Lycium barbarum polysaccharide and inhibition of UCA1 expression promote the proliferation of SH-SY5Y cells induced by MPP⁺ and inhibit apoptosis. Their combination has a more obvious effect on cell proliferation and apoptosis. The mechanism may be related to inhibition of mitochondrial apoptosis.