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A validated hydrodynamic-biogeochemical model was applied to investigate the effects of physical forcing (i.e., river discharge, winds, and tides) on the summertime dissolved oxygen (DO) dynamics and hypoxia (DO &lt, 3 mg L&minus, 1) in the Pearl River estuary (PRE), based on a suite of model sensitivity experiments. Compared with the base model run in 2006 (a wet year), the simulated hypoxic area in the moderate year (with 75% of river discharge of the base run) and the dry year scenario (with 50% of river discharge of the base run) was reduced by ~30% and ~60%, respectively. This is because under the lower river discharge levels, less particulate organic matter was delivered to the estuary that subsequently alleviated the oxygen demand at the water&ndash, sediment interface, and in the meantime, the water stratification strength was decreased, which facilitated the vertical diffusion of DO. Regarding the effect of winds, the highly varying and intermittent strong winds had a significant impact on the replenishment of bottom DO by disrupting water stratification and thus inhibiting the development of hypoxia. Sensitivity experiments showed that the hypoxic area and volume were both remarkably increased in the low wind scenario (with a bottom hypoxic zone extending from the Modaomen sub-estuary to the western shoal in Lingdingyang Bay), whereas hypoxia was almost absent in the strong wind scenario. The DO budget indicated that winds altered the bottom DO mostly by affecting the DO flux due to vertical diffusion and horizontal advection, and had a limited influence on the DO consumption processes. Moreover, the DO concentration exhibited remarkable fluctuations over the spring-neap tidal cycles due to the significant differences in vertical diffusion. The results of a tide-sensitivity experiment indicated that without tide forcing, most of the shallow areas (average water depth &lt, 5 m) in the PRE experienced severe and persistent hypoxia. The tides mainly enhanced mixing in the shallow areas, which led to higher vertical diffusion and enhanced replenishment of bottom DO.