It is an important practical problem to accurately recognize whether biological tissue is denatured during high intensity focused ultrasound (HIFU) treatment. Ultrasonic scattering echo signals are related to some physical properties of biological tissues. According to the characteristics of ultrasonic scattering echo signals, the recognition of denatured biological tissues is studied based on the variational mode decomposition (VMD) and multi-scale permutation entropy (MPE) in this paper. The ultrasonic echo signals are decomposed into various modal components by the VMD. The noise components and the useful components are separated according to the power spectrum information entropy of various modal components. The separated useful signals are reconstructed and the MPE are extracted. Furthermore, Gustafson-Kessel (GK) fuzzy clustering analysis is employed to obtain the standard clustering center, and the recognition of denatured biological tissues is carried out by Euclid approach degree and principle of proximity. The proposed method is applied to ultrasonic scattering echo signal during HIFU treatment. In order to determine the parameters of MPE algorithm for ultrasonic scattering echo signals, the embedding dimension of the MPE is discussed, and the scale factor of the MPE algorithm is optimized by genetic algorithm. When the delay time and the embedding dimension are 2 and 7 respectively, the MPE values decrease with scale factor increasing. Assuming that the scale factor is 12 from optimization results, the 293 ultrasonic scattering echo signals from normal tissues and denatured tissues are analyzed by the MPE. It is found that the MPE values of the denatured tissues are higher than those of the normal tissues. The MPE can be used to distinguish normal tissues and denatured tissues. Comparing with the recognition methods of the EMD-MPE-GK fuzzy clustering method and the VMD-WE-GK fuzzy clustering, the proposed method has good clustering performance and separability. Its partition coefficient (PC) is close to 1 and the Xie-Beni (XB) index is smaller. There are fewer feature points in the overlap region between MPE features of denatured tissues and normal tissues. The recognition results of denatured biological tissues in this experimental environment show that the recognition rate based on this method is higher, reaching up to 93.81%.