This paper focuses on Human-Object Interaction (HOI) detection, addressing the challenge of identifying and understanding the interactions between humans and objects within a given image or video frame. Spearheaded by Detection Transformer (DETR), recent developments lead to significant improvements by replacing traditional region proposals by a set of learnable queries. However, despite the powerful representation capabilities provided by Transformers, existing Human-Object Interaction (HOI) detection methods still yield low confidence levels when dealing with complex interactions and are prone to overlooking interactive actions. To address these issues, we propose a novel approach \textsc{UAHOI}, Uncertainty-aware Robust Human-Object Interaction Learning that explicitly estimates prediction uncertainty during the training process to refine both detection and interaction predictions. Our model not only predicts the HOI triplets but also quantifies the uncertainty of these predictions. Specifically, we model this uncertainty through the variance of predictions and incorporate it into the optimization objective, allowing the model to adaptively adjust its confidence threshold based on prediction variance. This integration helps in mitigating the adverse effects of incorrect or ambiguous predictions that are common in traditional methods without any hand-designed components, serving as an automatic confidence threshold. Our method is flexible to existing HOI detection methods and demonstrates improved accuracy. We evaluate \textsc{UAHOI} on two standard benchmarks in the field: V-COCO and HICO-DET, which represent challenging scenarios for HOI detection. Through extensive experiments, we demonstrate that \textsc{UAHOI} achieves significant improvements over existing state-of-the-art methods, enhancing both the accuracy and robustness of HOI detection.