Processes related to self-purification of Thi Nai lagoon has been studied in-situ and in laboratory in rainy season (October, 2013) and in dry season (May, 2014). Studied results shows that the capacity of self-purification of Thi Nai lagoon is quite good in rainy season, and the dominated process is material exchange. In dry season, due to the weak of material exchange, there is the accumulation of pollutants in water body, especial for nitrite, ammonium and phosphate. The studied results also indicate that the main processes that dominate the self-purification of Thi Nai lagoon are materials exchange, sedimentation, dispersion, decompose, and photosynthesis, respectively. The pollution loads discharged everyday into the Thi Nai lagoon is high, reducing the self-purification of lagoon, therefore it need to be controlled restrict.