Objective To explore the application value of non-bioartificial liver support system (NBALSS) in adult with acute liver failure (ALF). Methods Retrospective analysis of 92 patients with ALF admitted in Zhengzhou Sixth People’s Hospital from December 2023 to February 2026. According to treatment regimen, patients were divided into observation group (conventional medical therapy＋NBALSS, n＝46) and control group (conventional medical therapy alone, n＝46). In the observation group, plasma exchange (PE), dual plasma molecular adsorption system (DPMAS), or a combination of PE and DPMAS were selected based on the patient’s condition. Liver function, coagulation function, clinical efficacy, and survival at 10 weeks post-treatment were compared between the two groups before and after treatment. Results At 1 week and 2 weeks post-treatment, liver function indicators and coagulation function indicators in the observation group were superior to those in the control group (all P＜0.05). At 2 weeks post-treatment, the observation group achieved a significantly higher response rate compared with the control group (P＜0.05). At 10 weeks post-treatment, the observation group had a significantly lower short-term mortality rate than the control group (P＜0.05). Conclusion The NBALSS can effectively improve liver function and coagulation function in adult patients with ALF, increase treatment response rate and short-term survival rate.