In the search of bioactive compounds from marine sponges from Mauritius Waters, a preliminary cytotoxic assessment of their extracts was conducted. Marine sponges are important sources of secondary metabolites with the potential of treating human diseases such as cancer, a range of viral diseases, Alzheimer, malaria, and inflammations. The ethyl acetate, hexane and methanol extracts obtained from 26 species were evaluated at 50 µg/mL by MTT assay on HeLa, KB and HL-60 cancer cells. Statistical analysis showed that the ethyl acetate extracts had an average of 56.7% cytotoxicity and were more potent than hexane (44.2%) and methanol (33.4%) extracts. Further studies by MTS assay of selected extracts on KB cells showed IC50 values of 0.48 µg/mL, 85 ng/mL and 0.5 ng/mL for Biemna tubulata (BTUE), Epipolasis suluensis (ESE) and Hyrtios sp (HYSE) respectively. The IC50 values of BTUE, ESE and HYSE on HL-60 cells were 1.44 µg/mL, 2.28 µg/mL and 1.3 ng/mL respectively. HYSE was more active that BTUE and ESE as it displayed IC50 values at nano-level concentrations on KB and HL-60. HYSE induces early apoptosis at 2 ng/mL after 24 h treatment of HL-60 cells and the effect is dose-dependent without blockage of the cell cycle. Conversely BTUE and ESE elicited a moderate blockade of the cell cycle at the micromolar level associated with apoptosis. Further research is required to identify chemical components in HYSE, BTUE, and ESE.