Abstract: Described embodiments provide systems and methods for invalidating a cache of a domain name system (DNS) information based on changes in internet protocol (IP) families. A mobile device having one or more network interfaces configured to communicate over a plurality of networks using a plurality of internet protocol (IP) families is configured to maintain a cache storing DNS information of one or more IP addresses of a first IP family of the plurality of IP families used by the mobile device for a connection to a first network of the plurality of networks. The device can detect a change in the connection of the mobile device from the first network using the first IP family to a second network using a second IP family different from the first IP family and flush at least the DNS information of one or more IP addresses of the first IP family from the cache to prevent use by the mobile device of an IP address that corresponds to an invalid cache entry.