Cancer remains a global threat resulting in significant morbidity and mortality despite advances in therapeutic interventions, suggesting urgency for identification of anticancer agents. Crocodiles thrive in polluted habitat, feed on germ-infested meat, are exposed to carcinogenic heavy metals, are the very few species to survive the catastrophic Cretaceous-Paleogene extinction event, yet have a prolonged lifespan and rarely been reported to develop cancer. Therefore, we hypothesised that animals living in polluted environments such as crocodiles possess anticancer molecules/mechanisms.Crocodylus porosus was procured, blood collected, dissected and lysates prepared from internal organs. Organ lysates and sera were tested for growth inhibition, cytotoxic effects and cell survival against HeLa, PC3 and MCF7 cells and subjected to liquid chromatography mass spectrometry. RNA transcriptome analysis and differential gene analysis were performed using Galaxy Bioinformatics.Sera exhibited potent growth inhibition and cytotoxic effects against cancer cells. 80 molecules were detected from C. porosus and 19 molecules were putatively identified. Additionally, more than 100 potential anticancer peptides were identified from sera using bioinformatics based on peptide amino acid composition, binary profile, dipeptide composition and pseudo-amino acid composition. Following transcriptome analysis, 14 genes in treated HeLa cells, 51 genes in treated MCF7 cells and 2 genes in treated PC3 cells, were found to be expressed, compared with untreated controls.Animals residing in polluted milieus are an unexploited source for prospective pharmaceutical drugs, and could lead to identification of novel antitumour compound(s) and/or further understanding of the mechanisms of cancer resistance.