For the last years, different types of cucurbitacins have been extracted from various species of Cucurbitaceae family. For this review, all related papers were accumulated by searching electronic databases in the English language, including PubMed, Scopus, and Google Scholar. The keywords of cucurbitacin, cucumber anticancer therapy, cytotoxic effects, chemotherapy, and inhibitor effect were searched until February 2020. According to the result of this review, cucurbitacin E as a tetracyclic triterpenes compound, has been exhibited cell cycle arrest, anti-inflammatory and anticancer activities. It showed tumor proliferation prevention, induction of apoptosis or synergistically acts with other established antitumor compounds and cytokines throughout many molecular mechanisms. In a function-structure association manner, cucurbitacin E can inhibit Janus kinas2 (JAK2) phosphorylation, the signal transducer activator of transcription 3 (STAT3) and subsequently block these pathways, which seems to be the main mechanism of its activity. Future studies could target its detection in uninvestigated sources, subsequently its derivatives to improve their anticancer activity.