Brane construction with certain boundary conditions are used to study knot invariants and Khovanov homology. We argue that seven-dimensional manifolds in M-theory give rise to the topological theories may appear from certain twisting of the G-flux action. We discuss explicit constructions of the seven-dimensional manifolds in M-theory, and show that both the localization equations and surface operators appear naturally from the Hamiltonian formalism of the theories. Knots and link invariants are then constructed using M2-brane states in both the models.