"The next time the Syrians use their air defence systems against our planes we will destroy them without the slightest hesitation," Lieberman said on Israeli public radio.
Israeli warplanes hit several targets in Syria on Friday, with Prime Minister Benjamin Netanyahu saying the strikes targeted weapons bound for Lebanon's Shiite Hezbollah movement.
Syria's military said it had downed one of the Israeli planes and hit another as they were carrying out the pre-dawn strikes near the famed desert city of Palmyra that it recaptured from jihadists this month.
The Israeli military denied that any planes had been hit. The Syrian government has made similar claims in the past.
An Israeli army statement said "several anti-aircraft missiles" were fired following the raid but that none hit their targets.
One missile was intercepted by Israel's Arrow air defence system, Israeli media reported.
It was the most serious incident between the two countries since the Syrian civil war began six years ago.
In April 2016, Netanyahu admitted for the first time that Israel had attacked dozens of convoys transporting weapons in Syria destined for Hezbollah, which fought a 2006 war with Israel and is now battling alongside the Damascus regime.
"Each time we discover arms transfers from Syria to Lebanon we will act to stop them. On this there will be no compromise," Lieberman said Sunday.
"The Syrians must understand that they are held responsible for these arms transfers to Hezbollah and that if they continue to allow them then we will do what we have to do."
Israel does not usually confirm or deny individual raids, but it may have been led to do so this time by the circumstances of the incident.
President Bashar al-Assad's position has been strengthened in recent months with his forces reclaiming the whole of Syria's second city Aleppo, as well as enjoying continuing Russian support.
Lieberman said he did not wish "to interfere in the Syrian civil war or provoke a confrontation with the Russians" but that Israel's security would remain his top priority.
Israel seized most of the Golan Heights from Syria in the 1967 Six-Day War and annexed it in 1981, in a move never recognised by the international community.
Israel and Syria are still technically at war, though the border had remained largely quiet for decades until 2011 when the Syrian conflict began.
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