In response to vascular injury or alterations in the local environment, such as hypoxia and hypertension, contractile vascular smooth muscle cells (VSMCs) are able to switch to a synthetic phenotype characterized by increased extracellular matrix synthesis with decreased expression of contractile markers. miR‐182‐5p has recently been reported to play a regulatory role in VSMCs proliferation. However, little is known about its target genes and related pathways in VSMCs phenotypic switch. Here, we investigated the function of miR‐182‐5p in VSMCs phenotypic switch. The results showed that upregulation of miR‐182‐5p promoted the switching of VSMCs from a contractile to a synthetic phenotype under hypoxic conditions. Mechanistically, hypoxia elevated miR‐182‐5p, leading to a reduction in expression of contractile markers and weakened RhoA signaling. Using bioinformatics analysis, dual‐luciferase reporter assays and rescue assays, we demonstrated that miR‐182‐5p suppressed RhoA signaling by targeting RGS5. Collectively, the results from the present study indicated that miR‐182‐5p/RGS5/RhoA axis regulated hypoxia‐induced VSMCs phenotypic switch.