Objective To explore the value of detecting the levels of paraoxonase 1 (PON1), programmed death factor-1 (PD-1), and interferon gamma-induced protein-10(IP-10) in peripheral blood of patients with paraquat poisoning. Methods A prospective study was conducted in 120 patients with paraquat poisoning in the 980th Hospital of the Joint Logistics Support Force of Chinese people's Liberation Army from May 2017 to April 2023. The mortality and survival status of patients with paraquat poisoning within 30 days were statistically analyzed. The clinical data and peripheral blood PON1, PD-1, and IP-10 levels of patients with different prognoses were compared. Pearson correlation analysis was used to analyze the correlations of the peripheral blood PON1, PD-1, and IP-10 levels with the toxic dose, Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation System Ⅱ(APACHE Ⅱ). The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the peripheral blood PON1, PD-1, and IP-10 levels for the prognosis of patients with paraquat poisoning. Results During the follow-up period, a total of 35 patients died (29.17%), with the toxic dose, SOFA score, APACHE Ⅱ score, IP-10 level, PD-1 level of the dead patients were higher than those of the surviving patients, and the peripheral blood PON1 level was lower than that of the control group (P < 0.05). The correlation analysis showed that the level of PON1 in peripheral blood of paraquat poisoning patients was negatively correlated with the dose of poisoning, APACHE Ⅱ, and SOFA scores, while the levels of PD-1 and IP-10 were positively correlated with the dose of poisoning, APACHE Ⅱ, and SOFA scores (P < 0.05). The area under the curve (AUC) values for predicting paraquat poisoning using PON1, PD-1, and IP-10 were 0.738, 0.774, and 0.770, respectively. The combined prediction AUC value of the three was 0.922, which was significantly higher than that of each individual indicator. Conclusion Combined peripheral blood PON1, PD-1, and IP-10 testing in patients with paraquat poisoning is of high value in determining prognosis of patients.