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Human hair, as an emerging biological monitoring matrix, has begun to be used in various human exposure studies, but little research has been done on persistent organic pollutants (POPs), especially for the body burden of POPs in infants. In this study, 36 breast-fed infants in Shanghai were recruited for a study to determine their exposure to POPs, including 12 dioxin-like polychlorinated biphenyls (dl-PCBs), 6 indicator PCBs, and 8 polybrominated diphenyl ethers (PBDEs) in the inner layer (internal) and outer layer (external) of infant hair and human milk. The similarity or difference of the POP distribution pattern or concentration among these matrices was investigated, and only weak correlations (r < 0.4) were observed between the POP concentration in human milk and infant hair (internal or external). POPs in human milk have a different profile than those in infant hair, while they have stable concentration ratios (0.58–2.72), similar distribution patterns, fine Spearman’s rank correlations, and tangled principal component analysis (PCA) plots in each POP family between external and internal hair samples. The result suggested that POPs in internal hair can be easily affected by those in external hair, but POPs in human milk seem to have little contribution to the POP profile in internal hair. Although infant hair cannot reflect the POPs from diet or from body burden, it can be an ideal biomatrix that estimates infant exposure to POPs from exogenous sources like house dust when considering the similar pattern of POPs and their proper accumulation period in hair.