An efficient method is proposed for obtaining tetrahydrobenzo[a]xanthene-11-ones and tetrahydro-[1,3]-dioxolo[4,5-b]xanthen-9-ones. The method is based on the use of p-sulfonic acid calix[n]arenes as catalysts under solvent-free conditions. The antiproliferative activity of fifty-nine xanthenones against six human cancer cells was studied. The capacity of all compounds to inhibit cancer cell growth was dependent on the histological origin of the cells. QSAR studies indicate that among compounds derived from β-naphthol the most efficient compounds against glioma (U251) and renal (NCI-H460) cancer cells are those having higher hydrogen bonding donor ability.