Objectives To generate the cardiac-specific human FAM55A transgenic mice，a model for the study of its function and effects on cardiomyopathy． Methods The expression of FAM55A gene in the heart tissues from wild type mice and cTnTR141W transgenic mice were analyzed by western blot． The expression of FAM55A in seven different organs was also detected by western blot． The transgenic vector was constructed by inserting the human FAM55A gene into the downstream of α-MHC promoter． The transgenic mice were created by the method of microinjection． The genotype of transgenic line was identified by PCR and the expression level of the gene was determined by Western blot． The pathologic changes of the heart structure and function were analyzed by echocardiography and microscopy． Results The expression of FAM55A was up-regulated in the mice with DCM． One line of C57BL /6J transgenic mice with high human FAM55A expression was identified from five transgenic founders． Compared with the wild type mice，FAM55A transgenic mice showed increased left ventricular anterior wall during systolic and left ventricular anterior wall during diastole from one month of age to five months of age． The cardiac function of transgenic mice was increased at three months of age． The cardiomyocytes from transgenic mice exhibited hypertrophy and no disarrange under light microscope． Conclusions The expression of FAM55A was up-regulated in the cTnTR141W transgenic mice． The transgenic mice with cardiac-specific expression of the human FAM55A gene were generated and it can be used to crossbreed with the DCM model to investigate the effect of FAM55A gene on the development of cardiomyopathy．