The invention discloses a characteristic protein marker composition for screening thalassemia, a mass spectrum model and application thereof. The invention firstly discloses a characteristic protein marker composition for screening thalassemia. The composition comprises alpha globin, beta globin, delta globin, gamma globin and/or carbonic anhydrase I, and the sequences of the alpha globin, the beta globin, the delta globin, the gamma globin and/or the carbonic anhydrase I are respectively shown as SEQ ID NO.1-5. The invention further discloses a mass spectrum model containing the marker composition and application of the mass spectrum model in preparation of products for screening thalassemia. Based on the MALDI-TOF mass spectrum technology, the method can screen beta thalassemia by analyzing the mass spectrum peak areas and ratios of different characteristic proteins, carries alpha and beta thalassemia, alpha thalassemia and abnormal hemoglobin samples, and has the characteristics ofsimple sample pretreatment, high detection flux, less reagent consumables, low cost, less sampling amount, high sensitivity and the like; and large-scale population screening can be carried out in regions with high occurrence rate of thalassemia.