The mechanisms of rotavirus entry into the target cell are described as a multi-step event in which the virions are bound to sialic acid (SA), followed by interaction with heat shock cognate protein 70 (Hsc70), some integrins and protein disulfide isomerase (PDI).However, the cell surface receptor molecules facilitating the entry of tumor cell-adapted rotavirus are not completely characterized.Using infection blocking assays with antibodies to some heat shock proteins (HSPs) and also some inhibitors of these cellular proteins, we were able to identify the cell surface Hsp90, Hsp70, Hsc70, Hsp60, Hsp40, PDI and integrin β3 as receptors of tumor cell-adapted rotavirus in Reh cells.Furthermore, the results also indicated that these rotavirus receptors are associated with lipid microdomains (rafts).Our findings provide evidence that rotavirus tropism for these human acute lymphocytic leukemia cells is explained by the relatively high expression of some HSPs in rafts.The results shown here encourage further research aim at evaluating the potential use of rotaviruses as an oncolytic agent for the treatment of some cancers.