Cancer stem cells (CSCs) comprise a diminutive population of the tumor but pose major obstacles in cancer treatment, often their presence being correlated with poor prognosis, therapeutic resistance and relapse. Nanocarriers of combined drugs regimes demonstrate improved pharmacokinetics and decreased systemic toxicity by targeting the bulk tumor cells along with CSCs, holding the key to future successful chemotherapy. Herein, we developed lipid nanocapsules (LNCs) with co-encapsulated paclitaxel (PTX) and salinomycin (SAL) to eliminate breast cancer cells (MCF-7; non-bCSCs) and cancer stem cells (bCSCs) respectively. LNCs loaded with either PTX or SAL alone or in combination were fabricated by the phase inversion temperature (PIT) method. Physicochemical properties such as nano-size (90 ± 5 nm) and spherical morphology of LNCs were confirmed by dynamic light scattering (DLS) and scanning electron microscopy (SEM) respectively. More than 98 % encapsulation efficiency of drug, alone or in combination, and their controlled drug release was obtained. Drug loaded LNCs were efficiently internalized and exhibited cytotoxicity in non-bCSCs and bCSCs, with dual drug loaded LNCs offering superior cytotoxicity and anti-bCSCs property. Drug loaded nanocapsules induced apoptosis in bCSCs, potentiated with the co-delivery of paclitaxel and salinomycin. Synergistic cytotoxic effect on both cells, non-bCSCs and bCSCs and effective reduction of the tumor mammospheres growth by co-encapsulated paclitaxel and salinomycin suggest LNCs to be promising for treatment of breast cancer. © 2021 Elsevier B.V.