The invention discloses a use of a PH homeodomain family A member 3 (PHLDA3) in treatment on cardiac hypertrophy and belongs to the field of gene functions and application. The invention determines a relationship between expression of a PHLDA3 gene and cardiac hypertrophy and the relationship comprises that inhibition of PHLDA3 expression significantly promotes cardiac hypertrophy and fibrosis and deteriorates cardiac functions and promotion of PHLDA3 expression significantly inhibits cardiac hypertrophy and fibrosis and improves cardiac functions. Therefore, PHLDA3 can be used to screen and prepare drugs for protecting cardiac functions, resisting myocardial fibrosis and/or preventing, relieving and/or treating cardiac hypertrophy. The PHLDA3 provides a novel approach for treatment on cardiac hypertrophy.