Background: Cervical cancer is one of the most commonly diagnosed neoplasms and a leading cause of cancer death among females worldwide. Limitations with conventional medical treatments have driven researchers to search for alternative approaches using natural products. This study aimed to detemine potential anti-proliferative effects of methanol and water extracts of Pyrrosia piloselloides (P. piloselloides) on the HeLa cell line. Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine IC50 concentrations and apoptosis analysis was by flow cytometry. To identify chemical compounds in the extracts, gas chromatography-mass spectrometry (GC-MS) was employed. Results: P. piloselloides methanol extracts (PPME) showed antiproliferative effects on HeL awith an IC50 of 16.25μg/mL while the P. piloselloides water extract (PPWE) was without influence. Neither extract showed any significant effects on apoptosis. GC-MS analysis, revealed 5-hydroxymethylfurfural (23.1%), allopurinol (8.66%) and 3, 5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (7.41%) as major components in the PPME, while sulfolan-3-ol (10.1%), linoleic acid (9.06%) and β-sitosterol acetate (7.98%) predominated in the PPWE case. Conclusion: This first study of P. piloselloides showed PPME to exert potent anti-proliferative effect on HeLa cell lines. Further research now needs to be performed to establish the mechanisms of inhibition.