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Optimizing the green use efficiency of cultivated land in the karst region of southwest China is crucial for promoting sustainable development of land resources and achieving harmony between humans and nature. Based on the epsilon-based measure model and geographically and temporally weighted regression methods, this paper investigated the spatio-temporal variation and influencing factors of cultivated land green utilization efficiency. The results indicated that: i) Cultivated land green utilization efficiency had slightly increased from 0.842 in 2000 to 0.866 in 2020. ii) The spatial pattern of cultivated land green utilization efficiency showed a significant positive correlation, with a "hotspot-not significant-coldspot" from north to south. iii) Its spatial heterogeneity had increased during the observation period, with high-efficiency areas shifting from northeast to north. iv) The proportion of agricultural economy, general public budget revenue, per unit cultivated land value had a positive impact on the cultivated land green utilization efficiency, while urbanization rate, per capita cultivated land area, land replanting index, average altitude had a negative impact. Moreover, the driving factors exhibited significant spatiotemporal heterogeneity. Therefore, it is necessary to promote technological progress and scientific research, implement funds and policies, leverage the leading role of high-efficiency areas, formulate differentiated development strategies, and thereby improve the green use efficiency of cultivated land. • Cultivated land green utilization efficiency had slightly increased. • The high-efficiency area distribution changed from northeast to due north. • The driving factors exhibited significant spatiotemporal heterogeneity. • The differentiated policies promote the effective use of cultivated land. [ABSTRACT FROM AUTHOR]