Acute-on-chronic liver failure (ACLF) is the most severe form of acutely decompensated cirrhosis and is characterized by the presence of intense systemic inflammation. Leucocyte quantification can serve as an indirect indicator of systemic inflammation. In our study, we investigated the predictive value of hematological ratios (neutrophils to lymphocytes, monocyte to lymphocytes, platelets to lymphocytes, lymphocytes to C-reactive protein, and neutrophils to lymphocytes and platelets) in acute decompensation (AD) and ACLF patients and their relation to disease severity and early mortality. We included 60 patients with ACLF and AD, and 30 cirrhotic controls. Clinical data were collected, and survival was followed for 1 and 6 months. Blood samples were analyzed at admission for differential leucocytes and assessed for liver and renal function tests. The leukocyte ratios were calculated and compared, and their correlation with liver function indicators and prognosis was assessed. All ratios were significantly higher in AD and ACLF patients compared to control (except for lymphocyte to C-reactive protein ratio which was significantly lower), and were positively correlated with Child-Pugh score, model for end-stage liver disease (MELD)-Na, and ACLF severity scores. Multivariate regression revealed that neutrophil to lymphocyte ratio, monocyte to lymphocyte ratio, and MELD-Na were independent prognostic factors of 1-month and 6-month mortality. A unique prognostic nomogram incorporating MELD-Na, neutrophil to lymphocyte ratio, and monocyte to lymphocyte ratio could be proposed for predicting prognosis in AD and ACLF patients. Cheap, easy, and noninvasive hematological ratios are introduced as a tool for early identification and risk stratification of AD and ACLF patients.