The invention relates to a serum protein marker group for diagnosing MODY (maturity-onset-diabetes of the young) and application thereof. The serum protein marker group comprises five proteins: apolipoprotein C-IV (APOC4), apolipoprotein a (LPA), a complement component C6 (C6), a blood coagulation factor v (F5) and thyroid binding globulin (SERPINA7). ITRAQ (isobaric tags for relative and absolute quantitation) are used to combine with an MALDI-TOF / MS technology to detect; mass spectrum detection shows that expression levels of the serum apolipoprotein C-IV, the apolipoprotein a, the complement component C6 and the blood coagulation factor v protein in serum of a MODY patient are obviously improved, and an expression level of the thyroid binding globulin in the serum of the MODY patient is obviously reduced. Mass spectrum MRM (multiple-reaction-monitoring) also verifies that the five proteins are abnormal in expression in serums of the MODY patient, type-1 and type-2 diabetics and a healthy control group, and are specific proteins.