Biofouling caused by mussel byssus adhesion to underwater surfaces poses significant ecological and economic challenges in freshwater ecosystems. However, effective management remains difficult due to limited understanding of how material properties influence byssus adhesion and the underlying mechanisms. In this study, we used the invasive golden mussel (Limnoperna fortunei) as a model fouling species to assess byssus adhesion on commonly used engineering materials, natural substrates, polymers, and marine antifouling materials. Adhesion tests revealed that golden mussels exhibited significantly stronger byssus adhesion - quantified by byssus production, adhesion rate, and adhesion strength - on engineering materials, natural substrates, and polymers compared to antifouling surfaces. Notably, marine antifouling materials such as silicone-oil-infused polydimethylsiloxane demonstrated potential antifouling properties in freshwater ecosystems. Surface characterization and regression analysis indicated that byssus adhesion correlated positively with metal content and surface charge (voltage potential) but negatively with hydrophobicity (contact angle). Additionally, transcriptome sequencing and mass spectrometry identified key adhesion-related proteins, including foot proteins (Fp-1, Fp-2, and Fp-14) and byssal protein Bp-3, as well as the metabolic pathway "protein digestion and absorption", which likely contribute to the observed differences in byssus adhesion. Based on these findings, we propose future antifouling strategies for freshwater ecosystems, including optimization of antifouling materials, surface modifications for underwater structures, molecular interventions targeting byssus adhesion, and tailored management approaches for different aquatic environments. Our study provides valuable insights into mussel-dominated freshwater biofouling and contributes to the development of sustainable antifouling strategies in broader aquatic ecosystems.