The important role of sialic acid in various biological phenomena is well-established. In order to further clarify the role of sialic acid in cell death induced by various stimuli, the present study compared the cell survival of the HBL-2 human diffuse large B-cell lymphoma cell line upon anticancer drug-induced cell death, with or without neununinidase pretreatment: Cell survival was assessed using flow cytometry. Upon treatment with doxorubicin or ctoposide, the HBL-2 cell viability decreased. In etoposide-induced cell death, the HBL-2 cells demonstrated nuclear fragmentation, which was consistent with morphologically apoptotic cells. In addition, a higher decrease in the cell viability of ctoposide-treated HBL-2 cells was observed in cells pretreated with neuraminidase compared with cells that were not pretreated. Furthermore, the caspase-3, caspase-8 and caspase-9 activities in etoposide-induced apoptosis demonstrated a greater increase upon ricuraminidase pretreatment compared with no neuraminidase pretreatment. In conclusion, cell surface sialylation appears to protect lymphoma cells from anticancer drug-induced apoptosis.