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In this work, an analytical strategy based on non-target screening of semi-volatile organic compounds and subsequent risk assessment for adult and child populations has been conducted for the first time in household indoor dust samples in Spain. The methodology was based on a microwave-assisted extraction followed by gas chromatography coupled to high resolution mass spectrometry determination, using a hybrid quadrupole-orbitrap analyzer. The procedure was applied to 19 residential indoor dust samples, collected in different Spanish regions (namely Galicia, La Rioja, Catalunya, the Balearic Islands, and the Valencian Region). From the generated data, 4067 features were obtained, of which 474 compounds were tentatively identified with a high level of identification confidence (probable structure by library spectrum match or confirmed by reference standard), using a restrictive set of identification criteria. Most of the identified chemicals were natural products, metabolites, additives, and substances with industrial applications in the field of foods, cosmetics, pharmaceuticals, pesticides, and plastics. Finally, risk assessment was carried out by applying the threshold of toxicological concern approach, showing that risk to adult and child populations associated with the presence of the identified substances in the indoor dust was not expected, although the existence of indoor environments with conditions of potential risk cannot be discarded under a worst-case scenario approach. [Display omitted] • Household dust is a complex mixture where hazardous pollutants are accumulated • Non-target screening and human risk assessment of SVOCs in indoor dust is conducted • The method is based on microwave-assisted extraction and GC-Q-Orbitrap HRMS • 19 indoor dust samples were analyzed and 474 SVOCs were tentatively identified • A worst-case scenario approach showed conditions of potential risk by dust exposure [ABSTRACT FROM AUTHOR]