<p>The multidrug-resistant pathogen <i>Candida haemulonii</i> (<i>Candidozyma haemuli</i>) can cause superficial and systemic infections in vulnerable individuals. The ability of <i>C. haemulonii</i> to interact with extracellular matrix (ECM) components remains largely unexplored. Herein, we investigated <i>C. haemulonii</i>’s capacity to bind to fibronectin and assessed how this ECM protein influences fungal adhesion and biofilm development. The results revealed that <i>C. haemulonii</i> yeasts can recognize and interact with soluble fibronectin in a dose-dependent and isolate-specific manner, as demonstrated by flow cytometry. Confocal microscopy confirmed that fibronectin-binding molecules are primarily localized at the periphery of the yeasts, indicating that the binding sites reside on the cell surface. Additionally, <i>C. haemulonii</i> exhibited significantly greater adhesion to polystyrene surface coated with immobilized fibronectin (48.8 ± 5.1 yeasts/microscopic field) compared to either uncoated (28.4 ± 6.5) or albumin-coated (28.7 ± 5.3) surfaces. Fungal biofilm formation was significantly reduced on fibronectin-coated surface in comparison to uncoated control, with both biomass and ECM production decreasing by about 50%, as evaluated by crystal violet and safranin staining, respectively. Western blot analysis revealed that <i>C. haemulonii</i> cells degraded fibronectin during biofilm development. Notably, cell-free biofilm supernatant was capable of cleaving soluble fibronectin; this degradation was partially inhibited by PMSF, indicating the involvement of serine proteases in this process. Corroborating this finding, zymography revealed two serine proteases (50 and 60&#xa0;kDa) capable of degrading immobilized fibronectin. Collectively, the results demonstrate that <i>C. haemulonii</i> possesses fibronectin-binding molecules that contribute to adhesion and play a critical role in the early stages of its pathogenic process.</p>