The present study applied nontargeted screening techniques as a novel approach to evaluate the tap water samples collected during the "4.11" tap water pollution incident occurred on April 11, 2014 in Lanzhou in west China. Multivariate analysis (PCA and OPLS-DA) of about 3000 chemical features obtained in extracts of tap water samples by ultrahigh-pressure liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) analysis showed significantly different chemical profiles in tap water from pollution regions versus reference regions during the event. These different chemical profiles in samples from different regions were not observed in samples collected during the nonpollution period. The compounds responsible for the differences in profiles between regions were identified as naphthenic acids (NAs) and oxidized NAs (oxy-NAs) after the sample extracts underwent bromination to explore saturations, dansylation to identify hydroxylations and corresponding MS/MS mode analysis. A consistent finding was further observed in the targeted analysis of NA mixtures, demonstrating that the Lanzhou "4.11" tap water pollution incident could be attributed to oil spill pollution, and NA mixtures would be a marker for oil contamination. Such evaluations can help to rapidly discriminate pollution sources in accidental pollution events and contribute to regular water monitoring management of water safety issues.