Phenol contamination is a common occurrence in aquatic environments in different parts of the world and strategies that utilize cheap and eco-friendly phytoremediation technologies are required to overcome associated environmental problems. In the present study, the submersed macrophyte Hydrilla verticillata (L.F.) Royle was exposed to different concentrations of phenol (0-200 mg L) to assess its potential in phenol treatment. H. verticillata efficiently degraded phenol in solutions with initial concentrations lower than 200 mg L. The adverse effects of phenol on physiological parameters of H. verticillata were also investigated after 7 d of phenol stress. In order to explore the effect of phenol on the metabolism of H. verticillata during phytoremediation, gas chromatography-mass spectrometry (GC-MS) was used to analyze endogenous soluble organic compounds. The results revealed the presence of greater than 60 soluble organic compounds in H. verticillata. In the process of phenol degradation, fatty acid composition and carbon number distribution were affected in the plants while unsaturated fatty acid content was significantly lower, and several compounds including aliphatic dicarboxylic acids and aromatic ketones were degraded while new compounds were synthesized by the plant. In summary, H. verticillata is a promising candidate for the phytoremediation of the phenol-contaminated aquatic system.