In order to solve the problems of diagnosis and forecast of spatial-temporal variability of hydrological characteristics of the Kuyalnik Liman (water level, salinity and temperature) which cause chemical and biological processes occurring therein, and, therefore, affect the properties of brine and therapeutic mud, a non-stationary 3D numerical hydrothermodynamic model Delft3D-FLOW was applied. The model can be applied for research of the features and forecasting of spatial-temporal variability of hydrological characteristics of the Kuyalnik Liman under the influence of natural and anthropogenic factors forming its hydrological regime. Such opportunity is also indicated by the results of adaptation of the model to the Kuyalnik Liman conditions and its validation that are specified in this work. The important role of accounting of small streams flowing into the liman and accurate setting of intensity of storm rainfall during modelling is also shown. It is found that at the time of storm winds with longitudinal directions in relation to the liman’s water surface, the difference of watermarks in its northern and southern parts may reach 0.35-0.4 m.