Background Paraquat is a non-selective herbicide that causes severe tissue damage in various organs including the liver and kidney. The aim of this study was to determine the trend of the liver and kidney injury in patients with paraquat poisoning. Methods This retrospective cross-sectional study was performed at the Khorshid Hospital referral poisoning emergency center. The medical records of all patients with acute paraquat poisoning admitted from March 2017 to October 2020 were reviewed. Demographic factors, liver and kidney function tests and outcomes were recorded. Patients were divided into two groups based on the outcome of mortality (death or survived). The two groups were compared in terms of changes in creatinine and liver enzymes during hospitalization. Results A significant difference in mean creatinine levels between the two groups was observed from the third day after admission. The peak median Cr was 3.5 mg/dl for deceased patients in day 6 and 1.47 mg/dl for survived patients on 4th day. Minor elevations of ALT and AST were present in those who died. Logistic regression analysis shows patients who had level of creatinine higher than normal from the 2nd to 6th day post overdose, the risk of mortality was 4.83 to 7.44 times more than patients with normal creatinine level. The mean (SD) area under the curve for outcome prediction was reported to be excellent for creatinine on the 8th day post overdose (85.7 ± 13.2). Creatinine was higher than 2 on the 8th day post ingestion and had a sensitivity 100% and specificity 85.7% for mortality prediction (P value, 0.05). Conclusions The risk of mortality secondary to paraquat ingestion was highly associated with a rise in creatinine. Minor elevations of ALT and AST were also present in those who died. The creatinine concentration on different days post overdose can be helpful in predicting the severity of poisoning especially when the serum paraquat levels are not available.