To investigate the clinical values of the differences between hematocrit and serum albumin (HCT-ALB) for evaluating the severity of patients with acute paraquat (PQ) poisoning. Patients with acute PQ poisoning admitted to the Second People's Hospital of Yunnan Province from January 2018 to December 2019 were enrolled, and healthy voluteers during the same period were selected as the control. The general information, poisoning dose and poisoning time of patients, as well as the HCT and serum ALB levels before blood product infusion, intravenous infusion, or hemopurification at admission were collected, and the HCT-ALB was calculated. According to the results of rapid semiquantitative test of PQ in urine at admission, the patients were divided into PQ low concentration group (0-10 mg/L) and PQ high concentration group (30-100 mg/L). The relationship between poisoning time, poisoning dose, HCT-ALB and the degree of acute PQ poisoning were analyzed, and Spearman method was used to analyze the grade correlation. A total of 295 patients with acute PQ poisoning were enrolled, including 118 cases in PQ low concentration group and 177 cases in PQ high concentration group, and another 200 healthy persons matched with PQ patients in gender and age (healthy control group). The poisoning time of PQ low concentration group was significantly longer than that of PQ high concentration group [hours: 11.0 (6.0, 60.0) vs. 8.0 (5.0, 20.5), P < 0.01], but the poisoning dose was significantly lower than that of PQ high concentration group [mL: 10.0 (5.8, 15.0) vs. 40.0 (20.0, 80.0), P < 0.01]. The HCT and HCT-ALB in PQ low and high concentration groups were significantly higher than those of the healthy control group [HCT: (43.14±4.41)%, (43.54±5.40)% vs. (42.14±2.15)%, HCT-ALB: 3.59±6.26, 5.94±7.80 vs. -7.26±3.55, all P < 0.01], but ALB was significantly lower than that of the healthy control group (g/L: 39.54±5.74, 37.60±7.15 vs. 49.40±3.41, both P < 0.01). With the increase of urine PQ concentration, the HCT and HCT-ALB further increased, and ALB further decreased. There were significant differences between PQ high concentration group and PQ low concentration group [HCT: (43.54±5.40)% vs. (43.14±4.41)%, HCT-ALB: 5.94±7.80 vs. 3.59±6.26, ALB (g/L): 37.60±7.15 vs. 39.54±5.74, all P < 0.05]. The poisoning severity of patients with acute PQ poisoning were negatively correlated with poisoning time and ALB (r values were -0.195 and -0.695, respectively, both P < 0.01), there were positively correlated with poisoning dose, HCT, and HCT-ALB (r values were 0.650, 0.256, 0.737, respectively, all P < 0.01), and the correlation between HCT-ALB and poisoning severity was the strongest. The HCT-ALB can reflect the poisoning severity of patients with acute PQ poisoning and indirectly reveal the pathological changes of microvessels in patients with acute PQ poisoning.