Background/Aims: Gender differences of health-related quality of life (HRQoL) in patients with various disorders have been reported. Various nonmotor symptoms (NMSs) also affect the patients' lives and HRQoL, even in the early stages of Parkinson disease (PD). Our study aimed to identify whether there are gender differences of HRQoL in PD patients in the early stages, and which NMSs are associated with HRQoL depending on gender. Method: Eighty-nine PD patients (47 males, 42 females) and 36 healthy controls were enrolled. We evaluated HRQoL, NMSs, and their associations in each gender. Result: The total Parkinson Disease Quality of Life Questionnaire and Beck Anxiety Inventory scores were higher in female patients than in male patients. The correlation analysis revealed no association between NMSs and HRQoL in male patients. In female patients, HRQoL was highly correlated with depression, and moderately associated with fatigue. Conclusions: Gender differences of an association between HRQoL and NMSs exist in PD. We found that fatigue and depression were the main determinants of poor HRQoL in female patients even in the early stages. We suggest that a gender-specific therapeutic approach is important, and it is necessary to pay special attention to the predictors associated with causing poor HRQoL.