Paracetamol-induced hepatotoxicity is one of the most prevalent causes of drug-induced liver injury that may seriously end with fulminant liver failure so early prediction of acute liver injury seems to be helpful. This study aimed to evaluate the early predictive value of some hematological parameters as neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and red cell distribution width (RDW) in acute single paracetamol overdose. The study was conducted on 40 patients with acute paracetamol overdose presented to the Poison Control Center (PCC) of Minia University Hospital during the period from 1st February 2022 to 31st January 2023 and the patients were classified into 3 groups (mild, moderate and severe) based on the possibility of developing hepatotoxicity. The patient's mean age was 27.75 ± 7.3 years with female predominance (67.5%) and the majority came from urban areas (67.5%). Intentional drug overdose was the only mode of poisoning in all patients. A statistically significant difference was observed as regard the ingested dose which ranged from 5-15 gm. Elevated liver enzymes were recorded among patients of moderate and severe groups in the 2nd and 3rd days of admission. Statistically significant neutrophilia and lymphopenia was recorded with significant increase in NLR, PLR and MLR from the day of admission and during follow up in the moderate and severe groups. The average hospital stay was 4.2 ± 1.5 days and no mortality was recorded. The study demonstrated that NLR, PLR and MLR could act as early predictors of paracetamol-induced acute liver injury.