We performed a cross-sectional study of 82 Chinese patients with Parkinson's disease (PD) enrolled during an 18-month period using a clinical interview to assess the prevalence of nonmotor symptoms (NMS), the association with disease severity and motor status, and the impact on patients' health-related quality of life (Hr-QoL). The patients' NMS, Hr-QoL, disease severity, and motor status were assessed by the Nonmotor Symptoms Scale (NMSS), the 39-item Parkinson's Disease Questionnaire (PDQ-39), the modified Hoehn and Yahr staging scale (H&Y) and the Unified Parkinson's Disease Rating Scale part III (UPDRS III), respectively. We found that 100% of patients with PD presented with NMS. The NMSS significantly correlated with disease duration (Spearman's r(S) = 0.276, P = 0.012), H&Y (r(S) = 0.230, P = 0.038), and UPDRS III (r(S) = 0.350, P = 0.001). Similarly, the PDQ-39 SI significantly associated with the disease duration (r(S) = 0.258, P = 0.019), H&Y (r(S) = 0.340, P = 0.002), and UPDRS III (r(S) = 0.453, P < 0.001). NMS domains that influenced the PDQ-39 SI were sleep/fatigue, mood, gastrointestinal, urinary, and miscellaneous symptoms. This strongly suggested that the five domains played a key role in the manifestation of Hr-QoL. NMSS explains more of the variability in Hr-QoL than UPDRS III, when both are the model (stepwise multiple linear regression analysis R² change, 47.8% vs. 5.87%, respectively). Therefore, these findings demonstrate that NMS are independently and negatively associated with Hr-QoL in PD and that improving NMS should be viewed as an important part in the management of PD.