Background Cervical cancer is the third most prevalent cancer globally, with high incidence and mortality rates. Current treatments often result in severe side effects and drug resistance. While Solanecio mannii (S. mannii) roots have been traditionally used in cancer treatment, there is a lack of scientific validation of their anticancer potential. Therefore, the present study sought to analyze the metabolomics profile of the extracts and evaluate its anticancer and pro-apoptotic potential.Methods S. mannii roots were collected, freeze-dried, and extracted using diethyl-ether: methanol (v:v) for total extraction, and hexane and ethyl acetate for fractionation. This study analyzed the metabolomic profiles of S. mannii root extracts using gas chromatography coupled to mass spectrometry and evaluated their selective cytotoxic effect on human cervical cancer cell lines, specifically Henrietta Lacks (HeLa) cell lines. Moreover, this study investigated the extracts' potential to modulate autophagy and induce apoptosis. The pro-apoptotic effect of S. mannii was evaluated by analyzing chromatin morphological changes, the expression of Bcl-2 homologous antagonist/killer (BAK) and BCL2-Associated X (BAX) genes, and the activity of caspases.Results S. mannii exhibited selective anticancer and anti-proliferative activities against HeLa cells, with IC50 values of 113 +/- 0.28 mu g/mL for the total extract, 38.94 +/- 0.87 mu g/mL for the hexane fraction, and 12.16 +/- 0.52 mu g/mL for the ethyl acetate fraction. Additionally, S. mannii root extracts modulated autophagosome formation and autophagy-related genes. Furthermore, extracts exhibited an intrinsic pro-apoptotic potential by upregulating BAK and BAX and increasing the activity of caspase-9, -3, and -7 in a time- and dose-dependent manner. These effects are attributed to the bioactive phytocompounds identified in the extracts, including syringic acid, 4-coumaric acid, caffeic acid, vanillin, hydroquinone, oleic acid, beta-sitosterol, and stearic acid, among others.Conclusion This study showed the selective anticancer and pro-apoptotic activity of S. mannii root for the management of cervical cancer.