Abstract: The activation of fault/fracture zones (all replaced by faults below) induced by the long-section and multi-cluster fracturing for deep shale gas in Sichuan has caused frequent engineering problems such as casing deformation or frac-hits. Therefore, deep Luzhou block is taken as an example to analyze the mechanical conditions for fault activation induced by hydraulic fracturing. The results show that the critical stress state of high-angle developed faults is the internal cause of fault activation, and high construction pressure is the external cause of fault activation. Further, the mechanism of fault activation induced by long-section and multi-cluster fracturing is clarified: during the non-equilibrium propagation process of multi-cluster hydraulic fractures, when one cluster or several clusters are connected to a fault, they gradually develop into the dominant channel of fluid flow, and other clusters are suppressed or even stopped. The fault absorbs most of the fracturing fluids, leading to an increase in internal pore pressure of the fault and ultimately activation. Finally, three novel prevention strategy are proposed, including “short segment with few clusters”, “one blockage, one drainage”, and “fracturing cluster by cluster”. This achievement can provide guidance for solving casing deformation and frac-hits of shale gas in Sichuan.