Aim To elucidate the relation between NADPH oxidase Nox4 and the protective effect of fenofribate against cardiac hypertrophy. Methods Abdominal aorta coarctation (AAC)-induced hypertensive rats were constructed to observe the effect of fenofribate on left ventricular hypertrophy. Results Fenofribate could inhibit left ventricular hypertrophy in AAC-induced hypertensive rats. Compared with sham group, the mRNA and protein levels of NADPH oxidase Nox4 were significantly elevated in left ventricular tissue of AAC group; compared with AAC group, fenofribate reduced the mRNA and protein levels of NADPH oxidase Nox4 in left ventricular tissue in a dose-dependent manner.Conclusion Reducing NADPH oxidase Nox4 expression could be a crucial mechanism of fenofribate against hypertension-induced cardiac hypertrophy. It will provide further theoretical and experimental support for fenofribate curing hypertension- induced myocardial hypertrophy.