Santillana played 56 times and scored 15 goals for the Spanish national team, his debut being on 17 April 1975 in a 1–1 draw to Romania for the UEFA Euro 1976 qualifiers held in Madrid. He represented his country in the 1978 and 1982 FIFA World Cups, as well as three European Championships: 1976, reaching the quarter-finals, 1980, failing to advance to the second round, and 1984 which ended with a runner-up finish to hosts France, with the player coming close to scoring the opener on a header saved just off the line by Luis Fernández, of Spanish origin.