The fibrosis-4 index (FIB-4) is a non-invasive tool to assess fibrosis risk in chronic liver disease. We aimed to explore the relationship between the FIB-4 index and long-term major adverse cardiovascular events (MACE) in HCM patients. Consecutive patients diagnosed with HCM were included. Patients were divided into two groups using a defined cutoff value established through a ROC analysis for predicting MACE (FIB-4≥2.37 and FIB-4<2.37). The final analysis comprised 187 HCM patients (34.8% females, 66.49±11.43years of age), with 47 (25.1%) in the FIB-4≥2.37 group and 140 (74.9%) in the FIB-4<2.37 group. Among these, 147 (78.6%) individuals had complete follow-up data. Patients with FIB-4≥2.37 demonstrated a higher prevalence of co-morbidities such as atrial fibrillation (27.7% vs. 7.9%; P<0.001), heart failure (55.3% vs. 24.3%; P<0.001), elevated NT-proBNP levels (3.03±4.74 vs. 0.66±1.08; P<0.001), and lower LVEF (58.51±7.86 vs. 61.84±5.04; P=0.001). Over a median of 41 (IQR 16-63) months follow-up, MACE occurred in 49 (33.3%), with a significantly higher incidence in the FIB-4≥2.37 group (58.8% vs. 25.7%, P<0.001). Cardiac death rates were also elevated in the FIB-4≥2.37 group (20.6% vs. 2.7%, P=0.001). Cox regression analysis revealed an independent association between FIB-4≥2.37 and a higher risk of MACE (adjusted HR: 1.919, 95% CI 1.015-3.630; P=0.045) and cardiac death (adjusted HR: 9.518, 95% CI 1.718-52.732; P=0.010). Furthermore, the FIB-4 index shows positive correlations with left atrium diameter (r=0.229; P=0.003), septal thickness (r=0.231; P=0.002), posterior wall thickness (r=0.235; P=0.001), and NT-proBNP (r=0.271; P<0.001). Conversely, a negative correlation was observed between the FIB-4 index and left ventricular ejection fraction (r=-0.185; P=0.011). Elevated FIB-4 index, indicative of liver fibrosis, is independently associated with an increased risk of long-term MACE in HCM patients. This emphasizes the potential influence of liver function abnormalities on HCM prognosis, underscoring the need for comprehensive risk assessment in clinical management.