Anacardic acid (AA) is a natural active ingredient that accounts for 65% of the liquid extract from the shell of the cashew nut. Due to the stronger cytotoxic activity of hydrogenated AA (HAA) against NTERA-2 cancer stem cells (CSCs) than AA itself, HAA was co-conjugated with CD133 monoclonal antibody (mAb^CD133) into nanoliposomal particles (AMC). This nanoliposomal complex is expected to improved HAA activities against CSCs based on the targeting capacity of mAb^CD133 toward CD133, a typical CSCs’ surface marker. AMC was manufactured with a mean size of 100.9 nm, a zeta potential of −40.7 mV, and a PDI of 0.283. We report a 100% encapsulation efficiency of HAA into liposomes and a 90.7% conjugation efficiency with mAb^CD133. The penetration of AMC into NTERA-2 CSCs after 2 h was 83.7%. The AMC complex inhibited NTERA-2 growth with an IC50 (inhibition concentration at 50%) value of 75.83 ± 6.70 µM, showing the targeting ability and lower toxicity (IC50 > 100 µM) on healthy cells. The AMC nanoparticles also demonstrated significant potential apoptotic induction by activating caspase 3 activity by up to 2.57 and 2.06 folds compared to that of the negative control at 20 and 4 µM, respectively. This induction was significant improvement in comparison with that of unconjugated HAA (P <.05). AMC presented a clear effect on the solid structure of NTERA-2 spheroids and significantly suppressed the proliferation of CSCs in the 3D tumorspheres with an IC50 = 64.25 ± 3.15 µM, compared to the free form with an IC50 = 82.22 ± 0.65 µM (P <.05). Therefore, this nanoliposomal complex exhibits promising capacities as an effective material against NTERA-2 CSCs.