The present invention relates to a pharmaceutical composition for prevention and treatment of heart failure. Specifically, the present invention relates to a gene construct comprising a polynucleotide coding for SERCA2a protein or a fragment thereof and a polynucleotide coding for CCN5 protein or a fragment thereof, and a pharmaceutical composition comprising the same construct as an effective ingredient for preventing or treating heart failure. A pharmaceutical composition for prevention and treatment of heart failure according to the present invention is used in a method for co-expression of SERCA2a protein and CCN5 protein. Designed to exert a synergistic therapeutic effect through SERCA2a protein's function of preventing the loss of cardiomyocytes and increasing the activity of cardiomyocytes and CCN5 protein's function of suppressing the fibrosis of heart cells and tissues, the pharmaceutical composition can be useful for preventing or treating heart failure, which is a complex disorder induced by various etiological factors.