To investigate the influencing factors of lower limb amputation in patients with diabetic foot ulcers. Patients with diabetic foot ulcers who were hospitalised in a tertiary general hospital in Guizhou Province from January 2019 to March 2022 were retrospectively collected. Sociological information of the general population, comorbidities, laboratory-related indicators, and information on the specialty situation, using univariate analysis and multifactor analysis, compared the influencing factors of amputation and non-amputee patients. A total of 205 patients with diabetic foot and 69 ampute patients (33.7%) were enrolled. The univariate analysis found that the decrease in HDL cholesterol levels was associated with the occurrence of lower extremity amputation, and logistic stepwise regression analysis showed that HDL-C was inversely correlated with the amputation rate of patients with diabetic foot ulcers, and the risk of amputation at low levels of HDL-C was 2.452 times higher than that of high-level HDL-C (95% CI: 1.105-5.846). Decreased HDL cholesterol levels are an independent predictor of amputation in patients with diabetic foot ulcers.amputation, diabetic foot ulcer, high-density lipoprotein cholesterol, risk factor Key Messages• Clinical management, nutritional support, and physical exercise for patients with diabetic foot ulcers are emphasized, and prevention of amputation is strongly recommended. • From January 2019 to March 2022, 205 patients with diabetic foot ulcers who were hospitalized in the Affiliated Hospital of Zunyi Medical University in Guizhou Province were analyzed by univariate and multivariate analysis. • HDL cholesterol was an independent risk factor for lower limb amputation in patients with diabetic foot ulcers in this study. • The amputation rate in this research was 33.7%.