PTHrP is expressed in more advanced, aggressive tumors, and may play an active role in cancer progression. This study investigated the effects of PTHrP on apoptosis after UV irradiation, Fas ligation, or staurosporine treatment in BEN human squamous lung carcinoma cells. Cells at 70% confluency were treated for 24 h with 100 nM PTHrP 1-34, PTHrP 38-64, PTHrP 67-86, PTHrP 107-139, or PTHrP 140-173 in media with serum, exposed 30 min to 0.9 mJ/cm² UV-B and maintained for another 24 h. Caspase 3, 8, and 9 activities increased 5-fold. Pretreatment PTHrP 1-34 and PTHrP 140-173 ameliorated apoptosis after UV exposure, as indicated by reduced caspase activities, increased cell protein, decreased nuclear condensation and increased clonal survival. Other peptides had no effect on measures of apoptosis or cell death. PTHrP 140-173 also reduced caspase activities after Fas ligation by activating antibody, but neither peptide had effects on caspase 3 or 9 activities after 1 µM staurosporine. These data indicate that PTHrP 1-34 and PTHrP 140-173 protect against death receptor-induced apoptosis in BEN lung cancer cells but are ineffective against mitochondrial pathways. PTHrP contributes to lung cancer cell survival in culture and could promote cancer progression in vivo. The mechanism for the protective effect against apoptosis remains to be determined.