The OntoNL Framework provides an architecture and re-usable components for automating as much as possible the building of natural language interfaces to information systems. In addition to the syntactic analysis components, OntoNL has semantic analysis components which exploit domain ontologies to provide better disambiguation of the user input. We present in this paper the algorithms used for semantic processing of the natural language queries, as well as an ontology-driven semantic relatedness measure developed for this purpose. We also present extensive evaluation results with different ontologies using human subjects.