The Estuary can be considered as a large-scale, natural biogeochemical laboratory, characterized by pronounced physicochemical gradients of nutrients, salinity, terrestrial organic matter inputs, and other parameters. In this study, the changes of planktonic microbes and fluorescent dissolved organic matter (FDOM) at a 24 hours' time-series site were analyzed to reveal their responses to the dynamic environmental changes in the Pearl River Estuary (PRE) mixing zone. At the same time, the molecular composition of solid-phase extracted dissolved organic matter (DOM) of these samples were analyzed by negative-ion electrospray ionization (ESI) Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). The results showed that a tyrosine-like component of FDOM was positively correlated with total archaea rather than bacteria, suggesting the archaea might either produce or catabolize those tyrosine-like FDOM. The tyrosine-like component was positively correlated with 92 molecular formulas, whose O/C value were significantly lower than those molecular formulas positively correlated with other four FDOM components (two humic-like component and two tryptophan-like components), suggesting the less oxidation degree of those archaea-associated FDOM. Our study revealed the close relationship between archaea and FDOM and extended our understandings about the importance of archaea in carbon cycling in estuarine systems.