Context: It has been suggested that menopause exerts a negative impact on women's health-related quality of life (HRQL). However, studies on associations between menopause and HRQL in middle-aged Chinese women and its influencing factors are still lacking. Objective: To specify changes in HRQL in the menopausal transition and investigate factors associated with HRQL in middle-aged Chinese women. Methods: This was a cross-sectional, community-based study involving 868 participants aged 40–60 years in Gongshu District, Hangzhou, Zhejiang, PR China. HRQL was evaluated by the Short-Form Health Survey (SF-36). The presence of menopausal symptoms was assessed by modified Kupperman Menopausal Index. Serum levels of estradiol and follicle-stimulating hormone were measured. Sociodemographic characteristics including education, employment, income, marriage, and place of residence were collected. Patient: None. Intervention: None. Main Outcome Measures: SF-36, modified Kupperman Menopausal Index, Sociodemographic characteristics. Results: The mean (SD) age of all participants was 50.83 (5.60) years. Significant differences were seen in domains of physical functioning, role-physical, bodily pain, general health and health transition by menopausal stage. The multiple regression analysis showed that the impact of menopause on HRQL was significant in domains of physical functioning, role-physical and health transition. Compared to premenopausal women, perimenopausal women had increased risks of having impaired functions in role-physical and health transition (OR 1.69, 95% CI 1.06-2.70 and OR 1.79, 95% CI 1.16-2.76, respectively). Women in postmenopausal stage were more likely to have impaired functions in physical functioning and health transition than women in premenopausal stage (OR 1.89, 95% CI 1.25-2.86 and OR 1.75, 95% CI 1.20-2.54, respectively). Menopausal symptoms including hot flashes/sweating, mood swings, muscle/joint pain, fatigue and insomnia were negatively associated with certain domains of HRQL (p < 0.05 for all). Being married or cohabiting was positively related to general health (p < 0.05). Being unemployed or retired was negatively associated with role-physical (p < 0.05). Conclusions: There was a deterioration in HRQL during menopausal transition in middle-aged Chinese women. The menopausal transition showed significant impact on HRQL, adjusting for menopausal symptoms and sociodemographic factors.