Background: Traditional medicinal plants have gained attention as a repository of pharmacologically active molecules. Extracts derived from Pluchea lanceolata (DC.) Oliv. and Hiern are reported to be antimalarial and can protect against chemical-induced neurotoxicity. There is limited research on solvents for extraction of metabolites from stem of P. lanceolata and their anti-cancer potential, which needs to be investigated. Objectives: The objective of the study was to investigate potency of stem powder, extracted in ethanol, methanol, aqueous, and phosphate buffer saline (PBS) solvents, for their phytochemical content, antioxidant potential, and in vitro antiproliferative nature in human cancer cell lines. Materials and Methods: The stem extracts of P. lanceolata were evaluated by phytochemical assays, antioxidant assays (2,2-diphenyl-1-picrylhydrazyl [DPPH] radical scavenging assay, hydrogen peroxide radical scavenging assay, nitric oxide radical scavenging assay, total antioxidant capacity, and assay of reducing power), and antiproliferative potential against cervical (ME-180 and HeLa) and hepatic (HepG2) carcinoma cell lines by MTT assay. Results: Quantification studies showed that the total phenolic content was in the range 7.44–38.91 mg GAE/g of stem extract, while the flavonoids were present in the range 29.05–109.62 mg QE/g of stem extract. Aqueous (DPPH antioxidant capacity assay±PVPP, H2O2 free radical scavenging method-PVPP, assay of reducing power+PVPP, and total antioxidant capacity-PVPP), methanol (H2O2 free radical scavenging method+PVPP, NO radical scavenging assay+PVPP, total antioxidant capacity-PVPP), and ethanol (NO radical scavenging assay-PVPP, assay of reducing power-PVPP) extracts had the highest antioxidant potential in respective assays. MTT findings demonstrated that the aqueous extract was more potent in ME-180 and HepG2 cell lines while the PBS extract caused maximal cytotoxicity in HeLa cells. HepG2 cells were more susceptible than ME-180 and HeLa cells for any of the extract or standard drug evaluated. Conclusion: Aqueous extract of P. lanceolata stem is the most promising extract for further cancer-cell toxicity.