Provided are a computer program product, system, and method for selecting one of a plurality of scanner nodes to perform scan operations for an interface node receiving a file request. A list includes a plurality of scanner nodes in a network and for each scanner node a performance value. One of the scanner nodes in the list is selected based on the performance values of the scanner nodes and the file is transmitted to the selected scanner node to perform a scan operation with respect to the file. Indication is received from the selected scanner node performing the scan operation whether a subset of code in the file matches code in a definition set. The file request is processed to result in execution of the file request based on the indication of whether the subset of code in the file matches a definition in the definition set.