To clarify whether the high-density lipoprotein cholesterol/C reactive protein (HDL-C/CRP) ratio can be used as a new prognosticator of all-cause mortality in patients with chronic heart failure (CHF) (New York Heart Association (NYHA) cardiac class III/IV).Retrospective study.Several papers have revealed that HDL-C and CRP can act as anti-inflammatory and pro-inflammatory factors, respectively, to affect disease progression in patients with heart failure, and the balance of the two has been shown to affect the prognosis of patients with heart failure with preserved ejection fraction (HFpEF), but none of the above studies involved patients with the more severe forms of heart failure with mildly reduced ejection fraction and heart failure with reduced ejection fraction; therefore, the present study is to extend the balance of HDL-C and CRP to the whole range of types of patients CHF to further confirm its importance.This study is from a single centre in Yunnan Province, China.After excluding ineligible patients, we finally included 1192 patients with CHF from January 2017 to October 2021.The primary outcome was all-cause mortality in patients with CHF between January 2017 and October 2021. No secondary outcome measures were performed.All patients were divided into four groups according to the quartiles of the HDL-C/CRP ratio. Using the Kaplan-Meier analysis, the risk of all-cause mortality was always the highest for Q1 (HDL-C/CRP<0.395) and the lowest for group Q4 (HDL-C/CRP≥3.4163). Cox univariate and multivariate regression analyses showed that HDL-C/CRP was consistently an independent risk factor for death from CHF. Based on the receiver operating characteristic curve, the area under the curve for HDL-C/CRP was 0.7254 (p<0.001), with a sensitivity of 65.5% and a specificity of 69.6%.The HDL-C/CRP ratio is an independent prognostic indicator of all-cause mortality in patients with CHF in NYHA cardiac function class III/IV, which has good specificity and sensitivity. Patients with lower levels of the HDL-C/CRP ratio are at a greater risk of death than patients with higher levels of the HDL-C/CRP ratio.© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.