The river-blocking effects of debris flows have become common in numerous catchments in response to climate and environmental changes, and these effects have caused multiple, overlapping, and interconnected chain reactions that have led to huge losses in alpine regions. Considering this issue, this article developed a quantitative method for the regional river-blocking hazard assessment of debris flows by analyzing the in-depth relations among river-blocking hazard formation processes, factors and evolution mechanisms. Taking the debris flows in the Parlung Zangbo Basin in China as a case study, a multidimensional analysis was performed to analyze the characteristics of the hazard sequence and its relationship with climate change, including changes in temperature and precipitation. Accordingly, a new step toward a more comprehensive hazard assessment is proposed by establishing both a model and a system for regional river-blocking hazard assessment to analyze the debris flow evolution processes and environmental dynamics. Specifically, the sources of loose material were quantitatively estimated by establishing mathematical models based on the geometrical characteristics of diverse moraines, and the debris flow runoff was scientifically determined by focusing on the analysis of moraine sources, the brittleness index of the sediment mass and the geomorphological connectivity. Next, through coupling with the hydrodynamic conditions of debris flows and river flows, methods were established to determine the blocking degree of debris flow hazards at the regional scale. Validated by a field study and a remote-sensing interpretation of actual debris flows, a debris-flow-induced river-blocking hazard map was obtained, and the assessment results were in accordance with the actual disaster situation. The analysis shows that the distribution of zones with high to very high levels of river blocking is closely correlated with the topographic characteristics and actual disaster sequences of debris flows. These findings suggest that the assessment results provide scientific support for engineering planning and hazard prevention in climate-sensitive areas; thus, the presented method may serve as pertinent guidance for regional river-blocking hazard assessments of debris flows in the Parlung Zangbo Basin and beyond.