A sponge of the family Axinellidae is a marine invertebrate with plenty of medical potential applications. The present study aimed to investigate the antioxidative, toxicity, and apoptotic effects of Axinella aruensis extracts and fractions, particularly from the Indonesian Kangean Islands. The sponge was extracted with methanol, then partitioned with hexane, ethyl acetate, butanol, and water. Each fraction was observed for its free radical scavenging properties to DPPH, toxicity, and apoptosis to HeLa and MCF-7 cell lines. Experimental results show that the ethyl acetate fraction provides the highest activity than the methanolic extract and other fractions. The ethyl acetate fraction gives a strong DPPH radical scavenging with an IC50 value of 27.724 ± 0.029 g/mL and is toxic to Artemia salina with an LC50 value of 24.711 ± 0.478 g/mL. Cytotoxic activity of ethyl acetate fraction against HeLa and MCF-7 cells provide IC50 values of 89.990 ± 2.133 g/mL and 94.143 ± 0.720 g/mL, and induced apoptosis in both cells with IC50 values of 96.659 ± 0.023 g/mL and 93.474 ± 0.013 g/mL. The butanol fraction also showed intense activity, which was relatively comparable to the methanolic extract, although both activities were lower than that of the ethyl acetate fraction. Based on the metabolites fingerprinting analysis results, the ethyl acetate fraction consists of brominated compounds suspected of strongly influencing its anti-cancer properties. The sponge A. aruensis is undergoing further analysis to isolate and characterize the active constituents in each fraction, and thus can be developed for potential anticancer treatment.