Spatial resolution defines the physical limit of microscopes for probing biomolecular localization and interactions in cells.Whereas synchrotron-based X-ray microscopy (XRM) represents a unique approach for imaging a whole cell with nanoscale resolution due to its intrinsic nanoscale resolution and great penetration ability,existing approaches to label biomolecules rely on the use of exogenous tags that are multi-step and error-prone.Here,we repurpose engineered peroxidases as genetically encoded X-ray-sensitive tags (GXET) for site-specific labeling of protein-of-interest in mammalian cells.We find that 3,3’-diaminobenzidine (DAB) polymers that are in-situ catalytically formed by fusion-expressed peroxidases are visible under XRM.Using this new tag,we imaged the protein location associated with the alteration of a DNA-methylation pathway with an ultra-high resolution of 30 nanometers.Importantly,the excellent energy resolution of XRM enables multicolor imaging using different peroxidase tags.The development of GXET enlightens the way to nanoscopic imaging for biological studies.