Objective：To explore the effects of Tomoregulin-1 on dilated cardiomyopathy（DCM）pathological progress in mice. Methods：The expression level of Tomoregulin-1 in the heart of wild-type and cTnTR141W DCM transgenic mice was detected by Western blot. The phenotype analysis of the non-transgenic littermates（NTG），heart-specific Tomoregulin-1 knockdown（Tomoregulin-1-kd），cTnTR141W and heart-specific Tomoregulin-1-kd×cTnTR141W double transgenic（DTG） mice at 2，4 and 6 months of age were analyzed by M-mode echocardiography and histopathologic examination. Results：The expression of Tomoregulin-1 was significantly increased in the heart of cTnTR141W DCM transgenic mice. M-mode echocardiography showed that the heart-specific Tomoregulin-1-kd mice presented thin-walled ventricles，larger left ventricular diameters and decreased cardiac function at 2，4 and 6 months of age compared with the NTG mice. The DTG mice presented significantly thin-wall ventricles and the tendency of larger left ventricular diameters and decreased cardiac function at 2，4 and 6 months of age compared with the cTnTR141W DCM mice. Myocardial disarray and fibrosis were clearly observed in the heart tissues from the Tomoregulin-1-kd mice compared with the NTG mice. The DTG mice presented more serious pathological phenotype compared with the cTnTR141W DCM mice. Conclusion：Transgenic low expression of Tomoregulin-1 accelerated DCM pathological progress in mice. Tomoregulin-1 may be an important modifier gene of DCM.