Accurate lesion segmentation is crucial for clinical diagnosis and treatment planning. However, lesions often resemble surrounding tissues and exhibit ill-defined boundaries, leading to unstable predictions in boundary/transition regions. Moreover, small-lesion cues can be diluted by multi-scale feature extraction, causing under- or over-segmentation. To address these challenges, we propose an Uncertainty-Aware Hypergraph Refinement Network (UHR-Net). First, we introduce an Uncertainty-Oriented Instance Contrastive (UO-IC) pretraining strategy that couples geometry-aware copy-paste augmentation with hard-negative mining of lesion-like background regions to improve instance-level discrimination for small and visually ambiguous lesions. Second, we design an Uncertainty-Guided Hypergraph Refinement (UGHR) block, which derives an entropy-based uncertainty map from a coarse probability map to guide hypergraph refinement. By splitting hyperedge prototypes into foreground and background groups, UGHR decouples higher-order interactions and improves refinement in ambiguous regions. Experiments on five public benchmarks demonstrate consistent gains over strong baselines. Code is available at: https://github.com/CUGfreshman/UHR-Net.