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One of the common symptoms of cancer is the cells growth abnormaly. Currently, cancer treatment was conducted by chemotherapy. Doxorubicin was commonly used for chemotherapy through the TOP2A inhibition pathway. However, long-term use of Doxorubicin is thought to have a negative impact in the form of cardiotoxicity and multi drug resistance. Cucurbitacin compounds are natural ingredients which are generally produced by the Cucurbitaceae family plant. There are various types of Cucurbitacin compounds which are generally believed to have anti-cancer activity. The aim of this study was to explore the potential for anti-cancer in various types of Cucurbitacin compounds using in silico approach. DNA topoisomerase 2-alpha protein (TOP2A) was obtained from Protein Database (GDP) while a model of the compounds Doxorubicin and Cucurbitacin A, B, C, D, E, F, and I was collected from the chemical molecule database (PubChem). Molecular docking analysis was carried out using PyRx, while the analysis of DNA topoisomerase 2-alpha interaction with each ligand was analyzed by PyMol. The results showed that in general the whole Cucurbitacin compound tested had potential as an anti-cancer compound, with the highest bond energy value of -9.0 in Cucurbitacin I. Those value was higher than the control which was only -8.9.