Late Tuesday night the military said that an undefined "projectile" was sacked from Gaza towards southern Israel.
The four were rushed to nearby Shifa medical center for treatment.
The rocket launches in the direction of Israel from the Gaza Strip were resumed after a three-month break after US President Donald Trump ordered to transfer the US embassy in Tel Aviv to Jerusalem on December 6 and recognized the city as the capital of the Jewish state.
Three Palestinians were lightly wounded in the strikes, the health ministry in Gaza said. In response to the rocket fire, the IDF targeted a number of terrorist infrastructure in the Gaza Strip.
Israel allows goods to be brought into and out of Gaza on a daily basis, under heavy supervision, through the Kerem Shalom Crossing.
"The IDF holds the Hamas terror organization accountable for this hostile act originating in the Gaza Strip", said the IDF following its response.
The air force fired missiles into a site, run by the al-Qassam Brigades, the armed wing of Hamas, southwest of Khan Younis, in the southern part of the Gaza Strip.
The IDF reported that it tracked progress of the tunnel even before it extended into Israeli territory utilizing "unique tools combined with advanced technology, intelligence and operational capabilities". Yesterday, an army statement gave Israel's reply to the latest fire.
Israel has denied claims from authorities in Gaza that it was responsible for the deaths of two Palestinian militants killed in an unexplained explosion.