Azpilicueta is a Basque surname. Notable people with this surname include the following:
- César Azpilicueta (born 1989), Spanish footballer, currently playing for Atlético Madrid
- Francis Xavier (1506–1552), born Francisco de Jasso y Azpilicueta, Roman Catholic missionary
- Martín de Azpilcueta (1491–1586), Spanish canonist, theologian and economist