Acute poisoning is a frequently encountered medical emergency in the emergency room, typically resulting from the incorrect use of drugs or pesticides, and is characterized by sudden onset of severe symptoms, often leading to fatalities. This research was to explore the effect of hemoperfusion first aid process reengineering on electrolyte disturbance, liver function and prognosis in patients with acute poisoning. From August 2019 to July 2021, 137 patients with acute poisoning who received first aid process reengineering were selected as the observation group, and 151 patients with acute poisoning who received routine first aid were selected as the control group. The success rate, first aid-related indicators, electrolyte, liver function, and prognosis and survival were recorded after first aid treatment. The observation group had a 100% effective rate on the third day of first aid, which was significantly higher than the control group (91.39%). The observation group also had shorter time for emesis induction, poisoning assessment, venous transfusion, consciousness recovery, opening of the blood purification circuit, and start of hemoperfusion than the control group (P < 0.05). Additionally, the observation group showed lower levels of alpionine aminotransferase, total bilirubin, serum creatinine, and urea nitrogen after treatment, and a significantly lower mortality rate (6.57%) than the control group (26.28%) (P < 0.05). Hemoperfusion first aid process reengineering in patients with acute poisoning can improve the success rate of first aid, shorten the time of first aid, improve the electrolyte disturbance, treatment effect, liver function and blood routine of the patients.