Glioblastoma is one the most aggressive types of brain cancers resistant to conventional anti-neoplastic drugs. Marine seaweeds possess valuable bioactive compounds for disease prevention and therapy, including for a number of cancers. Caulerpa lentillifera is a tropical marine seaweed containing various minerals and bioactive ingredients. This study demonstrated the activity of C. lentillifera hexane extract (CLHE) against A172 human glioblastoma cells. The extract exerted growth-inhibitory effects by inhibiting cell proliferation and inducing apoptosis. CLHE also induced ROS accumulation and altered mitochondrial membrane potential in A172 cells. Taken together, CLHE might be a potential anticancer agent for use against glioblastoma.