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This article presents the methodology for developing a statistical model for monitoring salinity intrusion in the Mekong Delta based on the integration of satellite imagery and in-situ measurements. We used Landsat-8 Operational Land Imager and Thermal Infrared Sensor (Landsat- 8 OLI and TIRS) satellite data to establish the relationship between the planetary reflectance and the ground measured data in the dry season during 2014. The three spectral bands (blue, green, red) and the principal component band were used to obtain the most suitable models. The selected model showed a good correlation with the exponential function of the principal component band and the ground measured data (R2 > 0.8). Simulation of the salinity distribution along the river shows the intrusion of a 4 g/L salt boundary from the estuary to the inner field of more than 50 km. The developed model will be an active contribution, providing managers with adaptation and response solutions suitable for intrusion in the estuary as well as the inner field of the Mekong Delta.