[Objective] The spatiotemporal changes and driving mechanisms of net primary productivity （NPP） in the Nanpan River basin of Southwest China were analyzed， in order to provide scientific basis and technical support for ecosystem restoration， water resource management， and optimization of ecological security patterns in the Nanpan River basin and similar mountain-karst ecological regions. [Methods] Based on the improved CASA model， optimal parameters-based geodetector （OPGD）， and geographically and temporally weighted regression （GTWR） model， this study employed Theil-Sen trend analysis， Mann-Kendall trend test， coefficient of variation， and Hurst index to analyze the spatiotemporal distribution characteristics， fluctuation degree， future change trends， interactive effects and driving mechanisms of multiple factors on vegetation NPP in the Nanpan River basin from 2001 to 2023. [Results] ① The vegetation NPP in the Nanpan River basin was predominantly characterized by high-value NPP areas 〔>800 g/（m²·a） （calculated by carbon）〕， accounting for 82.46% of the total river basin area， among which 85.52% of this region showed a continuous increasing trend. Analysis of the coefficient of variation （mean 0.11） indicated that the spatial distribution pattern remained relatively stable， and the persistence analysis of the Hurst index （mean 0.64） further confirmed that NPP changes in this region exhibited significant temporal persistence characteristics. ② OPGD model analysis revealed that the kernel normalized difference vegetation index （KNDVI） （q=0.464 8） and land use type （q=0.382 4） were the primary drivers of vegetation NPP in the Nanpan River basin， among which the interaction between KNDVI and other driving factors had greater explanatory power for NPP changes. ③ The results of GTWR model analysis revealed that the persistent positive driving effect of KNDVI on vegetation NPP across the entire region coexisted with the regional differentiation characteristics of human activities， while the influence of climatic factors such as solar radiation and precipitation on vegetation NPP continued to enhance. [Conclusion] Vegetation NPP in the Nanpan River basin exhibits an overall stable upward trend， driven by vegetation status， land use structure， and climatic conditions. KNDVI plays a central role in multifactor interactions and has become a key indicator affecting regional ecosystem productivity.