Newcastle disease virus (NDV) exhibits oncolysis in its natural form. This oncolytic virus (OV) has the potential to specifically infect, propagate, and lyse cancer cells while sparing the normal cells. This study was aimed to screen for oncolytic NDV strain isolated from poultry. A total of ten velogenic NDV strains were propagated in 10 day old embryonated SPF chicken eggs and allantoic fluid of these infected eggs was collected for further study. The virus enumeration was carried out by hemagglutination assay (HA) and end point dilution method. The cytopathic effect of ten NDV strains on cancer cell lines like MDA-MB-231, MCF-7, PC3, and A549 along with normal control cell line HEK293 was determined by MTT assay 72 hours post infection. These cell lines were infected with three doses (1, 0.1, and 0.01 MOI). DNA laddering effect of the screened NDV isolate was studied after infecting all cancer and normal cells at MOI 1. Morphological changes in MDA-MB-231 on infection with the screened NDV isolate were analyzed using H&E hematoxylin and eosin staining. The screened NDV isolate showed the maximum cytopathic effect i.e. 61.55% on MDA-MB-231 at MOI 1 but had no potent cytotoxic effect on HEK293. DNA laddering effect was observed which confirmed the mode of death to be apoptosis. All the observed morphological changes in MDA-MB-231 were typical of the cytopathogenic effects of NDV on cancer cell lines. In conclusion, the screened oncolytic NDV shows effective oncolysis against MDA-MB-231 cell line. However, further study is required to determine the exact mode of action involved.