Searching for controllable topological state by means of external stimuli in 2D material‐based van der Waals (vdW) heterostructures is currently an active field for both the underlying physics and practical applications. Herein, a vdW heterostructure formed by vertically stacking AlSb and InSe monolayers is designed and its stacking configuration, stability, electronic structure, and effect of external electric field are investigated using first‐principles calculations. The AlSb/InSe heterobilayer studied, possessing both dynamical and thermal stabilities, is direct bandgap semiconductor and forms a Z‐scheme heterojunction. With inclusion of spin–orbit coupling (SOC) and applying external electric field, the bandgap of AlSb/InSe heterobilayer decreases at first and then increases, and a trivial insulator to topological insulator phase transition is achieved. For the topological insulator phase, band inversion is ascribed to the strong SOC of p orbitals of Sb. In this work, the way is paved for the design and application of multifunctional nanoscale devices such as topological field‐effect transistor.