We developed a method using site-specific genetic code expansion strategy in conjunction with APEX2-mediated proximity labeling to decipher interactors of hPTMs in living cells via quantitative proteomics. The method allows site-specific incorporation of a PTM-modified amino acid into histones that fused to APEX2, facilitating the labeling of the PTM-modified histones to binding proteins in vivo. Thus, this system will be a promising alternative strategy for interpreting the interactomes of hPTMs in cellular contexts.