This study intended to develop a robust and sensitive method for simultaneous determination of polycyclic musks (HHCB and AHTN) and nitro musks (musk xylene (MX) and musk ketone (MK)) in water samples using optimized solid-phase extraction (SPE) by gas chromatography and mass spectrometry (GC-MS). The SPE procedure was optimized in terms of selections of SPE cartridge, sample pH, elution process, etc. The method detection limits (MDLs) were from 0.09 to 0.18 ng L(-1) for the analytes. The recoveries ranged from 88.3 to 104.1% in spiked deionized water and from 86.4 to 106.8% in groundwater samples, respectively. The proposed approach was also validated by detecting real samples. The results revealed that HHCB and AHTN were ubiquitous in the local aquatic matrices. Furthermore, nitro musks were found in some aquatic matrices, which is consistent with the fact that nitro musks are still being produced and applied in China.