Treatment of 2-naphthol with aldehydes and allyl tributyl stannane or anisole in the presence of AlCl3 at 0C to room temperature afforded its 1-alkyl derivatives in high yields (76–83%) within 4–8 h. The products were evaluated for their cytotoxic activity against four human cancer cell lines. The most potent compound (5d) showed IC50 of 1.2 ± 1.1, 1.6 ± 1.0, 0.9 ± 0.1, and 0.8 ± 0.4 lM against Hep G2, A549, MDA 231, and HeLa cell lines, respectively, and its activity was found to be comparable to that of doxorubicin.