The G2385R and R1628P polymorphisms of the leucine-rich repeat kinase 2 (LRRK2) gene have been reported to be associated with Parkinson's disease (PD), but no data are available on Han-Chinese population of south-eastern China. This study aimed to investigate whether G2385R and R1628P variants are associated with sporadic PD in this population. Total 1,060 subjects were enrolled; including 550 unrelated healthy controls and 510 patients with sporadic PD. Genotyping of polymorphisms was performed by PCR-restriction fragment length polymorphism analysis. All variant samples were sequenced for further confirmation. The results showed that the A allele of the G2385R variant was significantly enriched in sporadic PD patient group (4.8%) when compared with control group [1.1%; odds ratio (OR) 4.58, 95% confidence interval (CI) 2.42-8.65, P < 0.01]. However, no significant difference in the frequency of the C allele of R1628P polymorphism variant was observed between cases and controls (2.8 vs. 1.7%, OR 1.67, 95% CI 0.93-2.99, P = 0.08). In conclusion, this study provides the first evidence that G2385R polymorphism is a risk factor for sporadic PD in Han-Chinese population of south-eastern China.