Objective: To explore the correlation between serum insulin-like growth factor-1 (IGF-1), serotonin (5-HT) and tumor necrosis factor-α (TNF-α) levels and Parkinson’s disease (PD) with depression. Methods: A total of 40 patients with PD complicated with depression who were admitted to the hospital between January 2018 and December 2019 were selected and included in the depression group. Meanwhile, 40 patients with PD and without depression, and 40 healthy persons were selected and included in the PD group and the control group, respectively. Serum IGF-1, 5-HT and TNF-α levels in each group were determined. The relationship between serum indicators and depression was analyzed by Pearson correlation analysis. Logistic regression analysis was performed to analyze related factors of PD with depression. Results: There were significant differences in serum IGF-1, 5-HT and TNF-α levels between the depression group, the PD group, and the control group (P<0.05). Serum IGF-1 and 5-HT levels in the depression group were significantly lower than those in the control group and the PD group (P<0.05), but the level of TNF-α was higher than the control group and the PD group (P<0.05). Hamilton Depression Scale (HAMD) score was negatively correlated with serum IGF-1 and 5-HT levels (P<0.001), but was positively correlated with TNF-α levels (P<0.001). Serum IGF-1 and 5-HT levels were negatively correlated with TNF-α levels (P<0.05). Logistic regression analysis showed that time of receiving education, high serum IGF-1 and 5-HT levels were protective factors for PD with depression (P<0.05), while long course of disease and high serum TNF-α levels were risk factors (P<0.05). Conclusion: Serum IGF-1 and 5-HT levels are low and TNF-α level is high in patients with PD complicated with depression. Risk factors include long course of disease, high TNF-α level, low IGF-1 and 5-HT levels.