The comparative kinetic analysis of total hypericin (TH) extraction from the pre-extracted flowers of Hypericum perforatum carried out under simultaneous external physical field and cooling reaction system operational conditions (SEPFC) was performed. The kinetics curves of TH extraction in SEPFC were measured in the temperature range from T = 298 to 328 K. It was proved that presence of ultrasonic and microwave field cause increasing of the extraction rate compared to conventional isothermal extraction. The possibility of describing the kinetics of TH extraction in SEPFC with empirical (Elovich's model) and physically-based (film-theory model) were explored. The kinetic complexity of the process was examined with the differential isoconversional method. By applying the model-fitting method the proper kinetic model of TH extraction in SEPFC was found: [1- (1 - alpha)((1/3))](2) = k(M) . t. The values of the extraction rate constant (k(M)), activation energy (E-a) and pre-exponential factor (ln A) of TH extraction were calculated. The effect of ultrasonic and microwave field on (a) k(M); (b) E-a and (c) lnA of TH extraction was determined. The model mechanism of activation of hypericin molecule for extraction in SEPFC conditions was proposed. The values of wave number of resonant vibrations, vibration quantum number and anharmonicity parameter for the TH extraction are obtained. (C) 2020 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.