The existence of initial bias in parameter estimation is an important issue in controlling short-run processes in semiconductor manufacturing. Harmonic rule has been widely used in machine setup adjustment problems. This paper generalizes the harmonic rule to a new controller called general harmonic rule (GHR) controller in run-to-run process control. The stability and optimality of the GHR controller is discussed for a wide range of stochastic disturbances. A numerical study is performed to compare the sensitivity of the GHR controller, the exponentially weighted moving average (EWMA) controller and the variable EWMA controller. It is shown that the GHR controller is more robust than the EWMA controller when the process parameters are estimated with uncertainty.