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We investigated the relationship between dyslipidemia and drug-induced liver injury (DILI), especially the level of triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) in severe DILI. In this single-centered retrospective study, of 326 patients with DILI, 221 patients were analyzed. Control groups include medication using group and acute hepatitis B group. The relationship between dyslipidemia and DILI was estimated. Demographic and clinical features were analyzed. Dyslipidemia and TG/HDL-C ratios were compared between DILI and control groups, DILI mild group and severe group. The area under the receiver-operating characteristic curve (AUC) was used to evaluate the credibility of the relationship and to find cut-off points. Dyslipidemia is related to DILI when compared with medication using control group (AOR 4.60; 95% CI 2.81–7.54; P < 0.01) and compared with acute hepatitis B group (AOR 2.12; 95% CI 1.37–3.29; P < 0.01). Dyslipidemia is associated with the severity of DILI (AOR 25.78; 95% CI 7.63–87.1; P < 0.01). TG/HDL-C ratio is higher in DILI group than that of medication using control group, also higher in severe DILI group than that of mild DILI group. AUCs for TG/HDL-C ratio to indicate the severity of DILI was 0.89 (P < 0.05), the cut-off point was 2.35. Dyslipidemia and TG/HDL-C ratio were related to DILI occurrence. Severe liver injury in DILI was associated with dyslipidemia and elevated TG/HDL-C ratio. [ABSTRACT FROM AUTHOR]