This article introduces a novel method for deep-tissue hydrogel formation using X-ray-activated polymerization, which overcomes the limitations of traditional UV/Vis light-based techniques. The study highlights the challenges of UV/Vis light in penetrating tissues and causing DNA damage, while near-infrared light, though better, still lacks sufficient penetration depth, especially in bone. The proposed approach utilizes a low-dose X-ray-activated persistent luminescent phosphor, enabling on-demand in situ photo-crosslinking reactions and hydrogel formation in deep tissues, including thick bovine bone. The key innovation is the use of halloysite nanotubes (HNTs) as templates for synthesizing HNTs-based X-ray-activated visible persistent luminescent emitting phosphors (HNTs@YF3:Tb3+), which store energy upon X-ray excitation and release visible luminescence to trigger hydrogel formation. The phosphor is biocompatible, highly stable, and exhibits intense persistent luminescence. The system was validated through in vitro and in vivo experiments, demonstrating high biocompatibility and the potential for safe deep-tissue hydrogel formation. The study shows that the X-ray-activated polymerization method enables precise and controlled hydrogel formation in deep tissues, with significant implications for biomedical applications such as tissue repair, drug delivery, and bone regeneration. The method's ability to penetrate thick bone tissues represents a major advancement in the field of photo-crosslinking hydrogels, offering new possibilities for clinical applications. The findings suggest that X-ray-activated polymerization could revolutionize the treatment of deep-tissue and bone-related conditions by enabling precise, safe, and effective hydrogel formation.This article introduces a novel method for deep-tissue hydrogel formation using X-ray-activated polymerization, which overcomes the limitations of traditional UV/Vis light-based techniques. The study highlights the challenges of UV/Vis light in penetrating tissues and causing DNA damage, while near-infrared light, though better, still lacks sufficient penetration depth, especially in bone. The proposed approach utilizes a low-dose X-ray-activated persistent luminescent phosphor, enabling on-demand in situ photo-crosslinking reactions and hydrogel formation in deep tissues, including thick bovine bone. The key innovation is the use of halloysite nanotubes (HNTs) as templates for synthesizing HNTs-based X-ray-activated visible persistent luminescent emitting phosphors (HNTs@YF3:Tb3+), which store energy upon X-ray excitation and release visible luminescence to trigger hydrogel formation. The phosphor is biocompatible, highly stable, and exhibits intense persistent luminescence. The system was validated through in vitro and in vivo experiments, demonstrating high biocompatibility and the potential for safe deep-tissue hydrogel formation. The study shows that the X-ray-activated polymerization method enables precise and controlled hydrogel formation in deep tissues, with significant implications for biomedical applications such as tissue repair, drug delivery, and bone regeneration. The method's ability to penetrate thick bone tissues represents a major advancement in the field of photo-crosslinking hydrogels, offering new possibilities for clinical applications. The findings suggest that X-ray-activated polymerization could revolutionize the treatment of deep-tissue and bone-related conditions by enabling precise, safe, and effective hydrogel formation.