In the present work, we presented an efficient synthesis and anticancer activity evaluation of some new 3-R-6-(5-arylfuran-2-yl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles. We have shown that the proposed synthetic protocols provided the possibility to design triazolothiadiazoles diversity with a considerable chemical novelty. The structures of target substances were confirmed by using 1H NMR spectroscopy, mass spectrometry and elemental analysis. The synthesized compounds were selected by the National Cancer Institute Developmental Therapeutic Program for the in vitro cell line screening. Among all the substances tested, three compounds exhibited significant cytotoxic activity.