Echinoderms are capable of asexual reproduction by fission. An individual divides into parts due to changes in the strength of connective tissue of the body wall. The structure of connective tissue and the mechanisms of variations in its strength in echinoderms remain poorly studied. An analysis of transcriptomes of individuals during the process of fission provides a new opportunity to understand the mechanisms of connective tissue mutability. In the holothurian Cladolabes schmeltzii, we have found a rather complex organization of connective tissue. Transcripts of genes encoding a wide range of structural proteins of extracellular matrix, as well as various proteases and their inhibitors, have been discovered. All these molecules may constitute a part of the mechanism of connective tissue mutability. According to our data, the extracellular matrix of echinoderms is substantially distinguished from that of vertebrates by the lack of elastin, fibronectins, and tenascins. In case of fission, a large number of genes of transcription factors and components of different signaling pathways are expressed. Products of these genes are probably involved in regulation of asexual reproduction, connective tissue mutability, and preparation of tissues for subsequent regeneration. It has been shown that holothurian tensilins are a special group of tissue inhibitors of metalloproteinases, which has formed within the class Holothuroidea and is absent from other echinoderms. Our data can serve a basis for the further study of the mechanisms of extracellular matrix mutability, as well as the mechanisms responsible for asexual reproduction in echinoderms.