Abstract: In order to provide a method for carrying out efficient tobacco substitution in cigarette blend maintenance, a research on the basis of differential analysis of tobacco pyrolysis was conducted. A thermogravimetric database of 120 kinds of tobacco leaves was established by TGA (Thermogravimetric Analyzer) technology, and the pyrolysis differential between tobacco samples was analyzed via NRMSE (Normalized root mean squared error). In an exemplary experiment, 9 grades of tobacco leaves in the blend of cigarette brand A were substituted respectively by their counterparts with the nearest pyrolysis profiles selected from the said database. The substituted sample determined by pyrolysis profile was compared with a substituted sample determined by blender, the results showed that:1) The pyrolysis differential based sample had a smaller NRMSE of 3.44%, and NRMSE of the substituted sample determined by blender was 4.88% while compared with the original blend in terms of pyrolysis differential. 2) In terms of routine chemical components and sensory characteristics, the pyrolysis differential based sample was closer to those of the original blend; however, the physical indexes and the deliveries of tar, nicotine and CO of the two substituted samples were all close to the original blend. 3) In a verification experiment, 5 grades of tobacco leaves in the blend of cigarette brand B were to be substituted, 3 substituted schemes were determined on the basis of pyrolysis differential, and the results of sensory evaluation and cigarette smoke analysis indicated that the optimal substituted blend could satisfy the application requirements, which further suggested that the substituted scheme based on pyrolysis differential was comparable to blender's subjective substituted scheme.