An advanced process control (APC) system, an APC method, and a computer program product, which, when executed, performs an APC method are provided for incorporating virtual metrology (VM) into APC. The present inventions uses a reliance index (RI) and a global similarity index (GSI) to adjust at least one controller gain of a run-to-run (R2R) controller when the VM value of a workpiece is adopted to replace the actual measurement value of the workpiece. The RI is used for gauging the reliability of the VM value, and the GSI is used for assessing the degree of similarity between the set of process data for generating the VM value and all the sets of historical process data used for building the conjecturing model.