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• Synthetic effects of urban morphology on indoor and outdoor natural lighting. • Employing web crawler technology to obtain data of residential urban blocks. • Adopting optimization algorithm to enhance overall natural lighting quality. • Quantitative descriptions and extraction of morphology features of samples. • Validating design strategies through morphology modification of real cases. The qualities of indoor and outdoor natural lighting environments are important aspects of sustainable urban design, which are inseparable, especially in high-density cities. This study aimed to reveal the synthetic effects of mesoscale urban morphology on indoor and outdoor natural lighting environments and propose corresponding design strategies for the sustainability of cities. Through data mining, 1680 residential blocks in Hangzhou, China, were selected for simulation analysis; urban morphology indicators that have a significant influence on daylighting performance were extracted. A multi-objective optimization algorithm was adopted to explore the optimal morphological features of urban morphology within a typical site. The extracted features were verified by morphological modifications in real cases. 1) The floor area ratio had the most significant effect on indoor daylighting (p = -0.673), while density was the most influential indicator for outdoor environments (p = -0.406); 2) in a typical site, morphological optimization can effectively improve lighting quality, with the average daylighting factor and sky view factor increasing by 3.7 and 6.7%, respectively; 3) two design strategies can simultaneously improve the indoor and outdoor natural lighting: dispersing the overall building mass to the perimeter of the site and dispersing the slab buildings of large masses as much as possible. [ABSTRACT FROM AUTHOR]