The Tarim River Basin (TRB) is an extremely arid area in China, suffering from dry climate and intense human activities, which have brought about significant changes in ecological processes and then, led to serious ecological vulnerability (EV). This study proposes an assessment framework to evaluate EV and analyze its dynamic change in the TRB during 2005–2015. An integrated method is developed with the Fuzzy Analytic Hierarchy Process (FAHP) and the Pressure-State-Response (PSR) framework, which highlights impacts of nature and anthropogenic interference on the ecology. Specific management strategies are put forward based on the spatial recognition of ecologically vulnerable areas in the TRB. The EV is divided into four vulnerability levels including Light I, Medium II, Heavy III and Very heavy IV. Results show that the average EV is at Heavy III vulnerability level in the TRB in the last 2005–2015, and there has been an increasing trend in EV, which even has come up to the Very heavy IV vulnerability level in the year 2013–2015. As a whole, the EV displays a high-to-low gradient from east to west during the study period. Heavy III and Very heavy IV vulnerability levels, distributed in the East, mainly in the mainstream areas with characterization of frequent human interferences, tend to increase persistently. In contrast, Light I vulnerability level, mainly in the west source areas, shows a significant decline after 2010. Based on the results, some suggestions targeted at different vulnerable areas were proposed to help restore ecological environments by integrating legal managements with public efforts. The proposed methodology, reflecting the nature and human interaction on the EV is of practical use for the ecological restorations in the TRB. Display omitted •An integrated indicator system for specially assessment of ecological vulnerability (EV) is established.•The EV was largely aggravated in the Tarim River Basin (TRB) during 2005–2015.•The Heavy III level dominates throughout the TRB with a low-to-high spatial distribution from west to east.•Ecological restorations with different use control for different partitions are proposed.