Background <p>To explore the expression characteristics, diagnostic value, and regulatory role of miR-148b-3p in hypertensive patients with left ventricular hypertrophy (LVH), providing preliminary evidence for mechanism research and clinical intervention.</p> Methods <p>108 patients with hypertension, 105 patients with hypertension-related LVH, and 112 healthy controls were enrolled. Serum miR-148b-3p levels were detected by RT-qPCR. ROC curve analysis evaluated its diagnostic value, and logistic regression identified risk factors for hypertension with LVH. H9c2 cell experiments and Ang II-induced myocardial hypertrophy models were used to verify miR-148b-3p’s functional role via CCK-8 (cell viability) and ELISA (ANP/BNP levels).</p> Results <p>Serum miR-148b-3p was higher in the hypertension with LVH group than in the hypertension and healthy controls. miR-148b-3p could effectively distinguish hypertensive patients with LVH (AUC = 0.821, 95%CI: 0.761–0.882). Additionally, elevated miR-148b-3p expression emerged as an independent risk factor for LVH and was strongly positively correlated with LVMI. In cellular experiments, overexpressing miR-148b-3p led to reduced cell proliferation and increased ANP and BNP expression; in contrast, the miR-148b-3p inhibitor reversed the above effects and alleviated Ang II-induced myocardial hypertrophy. Mechanistically, miR-148b-3p promotes myocardial hypertrophy by directly targeting KLF4.</p> Conclusions <p>miR-148b-3p is highly expressed in hypertension with LVH, has diagnostic potential, and promotes myocardial hypertrophy by targeting KLF4 and regulating cell function, serving as a novel molecular marker and therapeutic target.</p>