In this paper the Lie symmetry and Noether conserved quantity of a discrete difference sequence Hamilton system with variable mass are studied. Firstly, the difference dynamical equations of the discrete difference sequence Hamilton system with variable mass are built. Secondly, the determining equations and the definition of Lie symmetry for difference dynamical equations of the discrete difference sequence Hamilton system under infinitesimal transformation groups are given. Thirdly, the forms and conditions of Noether conserved quantities to which Lie symmetries will lead in a discrete mechanical system are obtained. Finally, an example is given to illustrate the application of the results.