ABSTRACT The simulation of large deformation contact problems has been a tough subject due to the existence of multiple nonlinearities, including geometric nonlinearity and contact interface nonlinearity. In this paper, we develop a novel method to compute the large deformation of 2D frictionless contact by employing Nitsche-based isogeometric analysis. The enforcement of contact constraints as one of the main issues in contact simulation is implemented by using Nitsche’s method, and the node-to-segment scheme is applied to the contact interface discretization. We detailedly derive the discrete formulations for 2D large deformation frictionless contact where NURBS is used for geometrical modeling and the Neo-Hookean hyperelastic materials are applied to describe the deformation of the model. The collocation method with Greville points is employed to integrate the contact interface and the classical Legendre–Gauss quadrature rule is used for contact bodies’ integration. The Lagrange multiplier method and penalty method are also implemented for comparison with Nitsche’s method. Several examples are investigated, and the obtained results are compared with that from commercial software ABAQUS to verify the effectiveness and accuracy of the Nitsche-based isogeometric analysis.