Excessive fluorine accumulation poses a significant threat to soil ecology and even human health, yet its impact on soil fauna, especially earthworms, remains poorly understood. This study employed multi-omics and biomarkers to investigate high fluorine-induced biochemical changes that cause tissue damages in Eisenia fetida. The results demonstrated that earthworms exhibited obvious damage with fluorine addition exceeding 200 mg kg(-1), with stress levels escalating as fluorine contents increased. Further analysis of the underlying mechanisms revealed that fluorine could upregulate genes encoding mitochondrial respiratory chain complexes I-III and downregulate those for IV-V, leading to reactive oxygen species (ROS) accumulation despite antioxidant system activation. The resulting ROS interfered with deoxyribonucleoside triphosphate synthesis, prompting homologous recombination as the main DNA repair mechanism. Additionally, fluorine-induced ROS also attacked and disrupted protein and lipid related metabolisms ultimately causing oxidative damages. These cumulative oxidative damages from high fluorine contents subsequently triggered autophagy or apoptosis, resulting in tissue ulceration and epithelial exfoliation. Therefore, high fluorine could threaten earthworms by inducing ROS accumulation and subsequent biomolecule damages.