Our experiments initially observed that miR‐425‐5p levels were downregulated in both heart tissue and plasma of HF mice, and then demonstrated that miR‐425‐5p acts as an upstream regulator of the TGF‐β1/Smad signalling in inhibiting CFs activation, thereby mitigating TAC‐induced over‐activated fibrotic and hypertrophic response. The gene discussed is TGFB1; the disease is hydrops fetalis.