Aggressive forms of adult T-cell leukemia (ATL) respond poorly to conventional anticancer chemotherapy, and new lead compounds are required for the development of drugs to treat this fatal disease. Recently, we developed ATL cell-selective proliferation inhibitors based on a tetrahydrotetramethylnaphthalene (TMN) skeleton 1, and here we report the design and synthesis of silicon analogs of TMN derivatives. Among them, compound 13 showed the most potent growth-inhibitory activity towards the ATL cell line S1T, though its selectivity for S1T over the non-ATL cell line MOLT-4 was only moderate. This result, as well as computational studies, suggests that sila-substitution (C/Si exchange) is useful for structure optimization of these inhibitors.