Dyslipidemia is common in lupus nephritis (LN). However, the relationship between the total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio and LN remains unclear. This study was designed to investigate the association between the TC/HDL-C ratio and LN. This study included individuals diagnosed with LN between January 1, 1996 and December 31, 2018. Split by the optimal cutoff TC/HDL-C ratio value of the primary outcome, patients were divided into lower (<6.71) and higher (≥6.71) TC/HDL-C ratio groups. Multivariate Cox regression analysis and subgroup analyses were carried out to confirm the connection of the TC/HDL-C ratio with the adverse clinical outcomes in LN. A total of 818 patients with LN were followed up for a median of ten years and 129 (15.77%) experienced all-cause death and 119 (14.55%) reached adverse renal events. Kaplan-Meier survival analyses demonstrated that patients exhibited a higher TC/HDL-C ratio were more susceptible to all-cause death (P=0.003) and adverse renal outcomes (P=0.001) in LN. After adjustments, a higher TC/HDL-C ratio still exhibited significant correlations with all-cause death [hazard ratio (HR):1.51, 95% confidence interval (CI): 1.03-2.23; P=0.036] and adverse renal outcomes in LN patients [HR: 1.57, 95%CI: 1.05-2.36; P=0.028]. Further subgroup analyses revealed that LN patients who were male, younger than 40 years old or with estimated glomerular filtration rate under 60 ml/min/1.73m2 seemed to be more susceptible to adverse clinical outcomes (P<0.05). An elevated TC/HDL-C ratio exhibited significant associations with poor prognosis in LN. Patients with LN may benefit from further TC/HDL-C studies.