► A multi-residues multi-families method for the analysis of 31 emerging pollutants. ► An innovative, rapid and simple sample extraction based on QuEChERS. ► Analytical method allowing the determination of the analytes at the low ng/g range. ► Application of the method to real soil samples. The aim of this study was to develop an analytical method for the analysis of traces of hormonal steroids and veterinary and human drugs in soil. Thus, 31 substances were selected, including 14 veterinary products, 11 hormonal steroids and 6 other well-known human contaminant compounds. The procedure inspired by the quick, easy, cheap, effective, rugged and safe (QuEChERS) extraction method was developed. First the acetonitrile-based extraction was optimized. This step was followed by a solid-phase extraction (SPE) clean-up using both a strong anion-exchange cartridge and a polymeric cartridge. The analysis was then performed using liquid chromatography coupled to a triple quadrupole analyser operated with tandem mass spectrometry. This analytical procedure was validated using the ICH/2005 standard by evaluating the linearity (from 0.01ng/g to 1000ng/g –R2>0.99), the intra-day precision (relative standard deviation (RSD)<20%), the inter-day precision (RSD<30%), recoveries (40–110% for most of the compounds) and limits of detection and quantification. This method allowed for the determination of the target analytes in the lower ng/g concentration range. The methodology was then applied to real soil samples collected in several areas of France that received different manure or sludge treatments. Some target compounds were detected at very low level (inferior to the ng/g). Veterinary antibiotics, mainly from the sulfonamide family, were found in soils treated by manure (0.02–0.12ng/g). On the other hand, pharmaceuticals usually used by humans (carbamazepine, ibuprofen) were detected in soils treated by domestic sludge.