PurposesTo investigate health-related quality of life (HRQoL) of patients with knee osteoarthritis (KOA) in Guangzhou, China, and examine its association with selected sociodemographic characteristics as well as knee function.MethodsThis multicenter cross-sectional study included 519 patients with KOA in Guangzhou from April 1 to December 30, 2019. Data on sociodemographic characteristics were obtained using the General Information Questionnaire. The disability was measured using the KOOS-PS, resting pain using the Pain-VAS, and HRQoL using the EQ-5D-5L. The association of selected sociodemographic factors, KOOS-PS and Pain-VAS scores with HRQoL (EQ-5D-5L utility and EQ-VAS scores) were analyzed using linear regression analyses.ResultsThe median (interquartile range [IQR]) of EQ-5D-5L utility and EQ-VAS scores were 0.744 (0.571–0.841) and 70 (60–80) respectively, lower than the average HRQoL in the general population. Only 3.661% of KOA patients reported no problems in all EQ-5D-5L dimensions, with Pain/Discomfort being the most frequently affected dimension (78.805%). The correlation analysis showed that the KOOS-PS score, Pain-VAS score and HRQoL were moderately or strongly correlated. Patients with cardiovascular disease, no daily exercise, and high KOOS-PS or Pain-VAS scores had lower EQ-5D-5L utility scores; and patients with body mass index (BMI) > 28 ,high KOOS-PS or Pain-VAS scores had lower EQ-VAS scores.ConclusionsPatients with KOA had relatively low HRQoL. Various sociodemographic characteristics as well as knee function were associated with HRQoL in regression analyses. Providing social support and improving their knee function through methods such as total knee arthroplasty might be crucial to improve their HRQoL.