© 2020 Elsevier B.V.Porous, bioactive microspheres have always been a dream material to biomedical scientists for bone regeneration and drug delivery applications due to their interconnectivity, unique pore geometry, encapsulation ability and porosity spanning macroscopic, microscopic and nanoscopic length scales. Extensive efforts have been made to produce such materials synthetically at a great cost of money, time and labor. Herein, naturally-assembled multifunctional, open-channeled and hollow bioactive micro silica spheres (diameter 209.4 ± 38.5 µm) were discovered in a marine sponge (Geodia macandrewii), by peeling the outer surface of the sterrasters using hydrogen fluoride. The obtained micro silica spheres exhibited valuable characteristics such as homogeneously distributed pores, a cavity in the center of the sphere, and channels (approx. 3000) opening from each pore into the central cavity. Simulated body fluid analysis demonstrated the bioactivity of the micro silica spheres; whereas, no bioactivity was recorded for the original untreated sterrasters. The non-cytotoxicity and osteogenic ability of the isolated microspheres were confirmed through osteoblast cell culture. Finally, these silica based porous microspheres were tested for controlled drug release capacity. The spheres showed excellent loading and release abilities for an anti-cancer drug, carboplatin, in simulated solutions and in human cancer cell culture, HeLa, through a real time cell analyzer system. The drug loading capacity of the porous beads was determined as 10.59%. Considering the unique biological and physicochemical properties, these novel bioactive silica spheres, which we name as giant macroporous silica (GMS), are promising materials for a range of applications including bone tissue engineering and drug delivery.