Force is everywhere. Through cell-intrinsic activities and interactions with the microenvironment, cells generate, transmit, and sense mechanical forces, such as compression, tension, and shear stress. These forces shape the mechanical properties of cells and tissues. Akin to how balanced biochemical signaling safeguards physiological processes, a mechanical optimum is required for homeostasis. The brain constructs a mechanical optimum from its cellular and extracellular constituents. However, in brain cancer, the mechanical properties are disrupted: tumor and nontumoral cells experience dysregulated solid and fluid stress, while tumor tissue develops altered stiffness. Mechanosensitive (MS) ion channels perceive mechanical cues to govern ion flux and cellular signaling. In this review, we describe the mechanical properties of the brain in healthy and cancer states and illustrate MS ion channels as sensors of mechanical cues to regulate malignant growth. Targeting MS ion channels offers disease insights at the interface of cancer, neuroscience, and mechanobiology to reveal therapeutic opportunities in brain tumors.