Objective: We analyzed 953 patients from KNOW-CKD cohort who assessed HR-QOL by physical component summary (PCS) and mental component summary (MCS) of the SF-36 questionnaire at baseline and 5 years later. Overall HR-QOL was defined as the sum of PCS and MCS. A decline in HR-QOL was defined as a decrease of 10% or more in overall HR-QOL at 5 years. Participants were divided into estimated glomerular filtration rate (eGFR) categories (<30, 30‐44, 45-60, ≥60 mL/min/1.73 m2). Methods: After 5 years, 271 (28.4) patients developed the decline of HR-QOL. The incidence rates were higher in the lower eGFR groups (P<0.001). In multivariate logistic regression analysis, lower eGFR were associated with HR-QOL decline. The adjusted odds ratio for HR-QOL decline was 3.04 (1.83-5.06), 1.97 (1.26-3.07) and 1.23 (0.75-2.02) in eGFR (ml/min/1.73m2) categories of <30, 30-44 and 45-59 compared to ≥60. Results: Low baseline renal function was independent and significant risk factor for HR-QOL decline in predialysis CKD. These results suggest the importance of interventions to break the vicious cycle of HR-QOL decline and renal function decline. Conclusions: Objective: Health-related quality of life (HR-QOL) is an important predictor of renal function decline and high mortality in chronic kidney disease (CKD). Although several risk factors for low HR-QOL are known, the determinant of future HR-QOL decline are uncertain. We hypothesized that low renal function might be a risk factor for HR-QOL decline. The aim of this study is to verify the relationship between baseline renal function and the decline of HR-QOL in a predialysis CKD cohort. Methods: We analyzed 953 patients from KNOW-CKD cohort who assessed HR-QOL by physical component summary (PCS) and mental component summary (MCS) of the SF-36 questionnaire at baseline and 5 years later. Overall HR-QOL was defined as the sum of PCS and MCS. A decline in HR-QOL was defined as a decrease of 10% or more in overall HR-QOL at 5 years. Participants were divided into estimated glomerular filtration rate (eGFR) categories (<30, 30‐44, 45-60, ≥60 mL/min/1.73 m2). Results: After 5 years, 271 (28.4) patients developed the decline of HR-QOL. The incidence rates were higher in the lower eGFR groups (P<0.001). In multivariate logistic regression analysis, lower eGFR were associated with HR-QOL decline. The adjusted odds ratio for HR-QOL decline was 3.04 (1.83-5.06), 1.97 (1.26-3.07) and 1.23 (0.75-2.02) in eGFR (ml/min/1.73m2) categories of <30, 30-44 and 45-59 compared to ≥60. Conclusions: Low baseline renal function was independent and significant risk factor for HR-QOL decline in predialysis CKD. These results suggest the importance of interventions to break the vicious cycle of HR-QOL decline and renal function decline.