Objective This paper aims to investigate the correlation between apoptosis inducing factor mitochondria associated 2(AIFM2)and mitochondrial fusin 2(MFN2)with insulin resistance and progressive liver fibrosis in patients with metabolic-dysfunction-associated fatty liver disease(MAFLD).Methods A total of 120 patients with MAFLD who received medical treatment in Rugao People's Hospital from December 2020 to December 2022 were selected as the study objects(assigned to the observation group),and 120 healthy physical examination subjects who received physical examination in the same hospital during the same period were selected for the study(assigned to the control group).The general data of the two groups were collected,and the fasting venous blood was collected to determine the levels of fasting plasma glucose(FPG),fasting insulin(FINS),type Ⅳ collagen(CⅣ),type Ⅲ procollagen(PCⅢ),laminin(LN),hyaluronic acid(HA),and the expression levels of serum AIFM2 and MFN2.The fibrosis score of nonalcoholic fatty liver disease(NFS)was used to evaluate the degree of liver fibrosis.Those with NFS≥0.676 were included in the progressive liver fibrosis group(n=31)and those with NFS<0.676 were included in the non-progressive liver fibrosis group(n=89).Pearson correlation analysis was used to explore the relationship between the levels of serum AIFM2 and MFN2 and insulin resistance and liver fibrosis indexes in patients with MAFLD.The multivariate logistic regression model was used to analyze the risk factors of progressive liver fibrosis in patients with MAFLD.Results Compared with the control group,the average BMI and the average waist-hip ratio(WHR)of the observation group are higher,the expression levels of serum AIFM2 and MFN2 are lower,the levels of serum CⅣ,PCⅢ,LN,and HA are higher,the levels of FPG,FINS,and HOMA-IR are higher,with statistically significant differences(P<0.05).Pearson correlation analysis shows that the expression levels of serum AIFM2 and MFN2 in patients with MAFLD are negatively correlated with HOMA-IR(P<0.05),and the expression level of serum AIFM2 and MFN2 are negatively correlated with the levels of serum CⅣ,PCⅢ,LN,and HA(P<0.05).The expression levels of serum AIFM2 and MFN2 in the progressive fibrosis group are lower than those in the non-progressive fibrosis group,with statistically significant differences(P<0.05).The multivariate logistic regression model analysis shows that WHR,BMI,HOMA-IR,and serum AIFM2 and MFN2 are independent risk factors for progressive liver fibrosis in MAFLD patients(P<0.05).Conclusions Serum AIFM2 and MFN2 are both low in MAFLD patients,and are both closely related to insulin resistance and progressive liver fibrosis.Monitoring these indicators can provide effective information for clinical diagnosis and treatment,and is of great significance for improving prognosis and preventing complications.