The effective generalized orthogonal polynomials (GOPs) expansion is applied to estimating the parameters of a single-input-single-output linear time-varying system. It is based on the integration operational matrix for GOPs, which can represent all kinds of individual orthogonal polynomial. Using the concept of GOP expansion for a state function and a control function, the differential input-output equation is converted into a set of overdetermined linear algebraic equations. The unknown parameters are evaluated by a weighted least-squares method. An illustrative example is given. Very accurate results are obtained.