The pollution on the Thi Vai River has been spreading out rapidly over the two lasted decades caused by the wastewater from the industrial parks in the left bank of Thi Vai River and Cai Mep Estuaries. The evaluation of the benthic macroinvertebrate changes was very necessary to identify the consequences of the industrial wastewater on water quality and aquatic ecosystem of Thi Vai River and Cai Mep Estuaries. In this study, the variables of benthic macroinvertebrates and water quality were investigated in Thi Vai River and Cai Mep Estuaries, Southern Vietnam. The monitoring data of benthic macroinvertebrates and water quality parameters covered the period from 1989 to 2015 at 6 sampling sites in Thi Vai River and Cai Mep Estuaries. The basic water quality parameters were also tested including pH, dissolved oxygen (DO), total nitrogen, and total phosphorus. The biodiversity indices of benthic macroinvertebrates were applied for water quality assessment. The results showed that pH ranged from 6.4 – 7.6 during the monitoring. The DO concentrations were in between 0.20 - 6.70 mg/L. The concentrations of total nitrogen and total phosphorous ranged from 0.03 - 5.70 mg/L 0.024 - 1.380 mg/L respectively. Macroinvertebrate community in the study area consisted of 36 species of polychaeta, gastropoda, bivalvia, and crustacea, of which, species of polychaeta were dominant in species number. The benthic macroinvertebartes density ranged from 0 - 2.746 individuals/m−1 with the main dominant species of Neanthes caudata, Prionospio malmgreni, Paraprionospio pinnata, Trichochaeta carica, Maldane sarsi, Capitella capitata, Terebellides stroemi, Euditylia polymorpha, Grandidierella lignorum, Apseudes vietnamensis. The biodiversity index values during the monitoring characterized for aquatic environmental conditions of mesotrophic to polytrophic. Besides, species richness positively correlated with DO, total nitrogen, and total phosphorus. The results confirmed the advantage of using benthic macroinvertebrates and their indices for water quality assessment.