Michael Fallon has said British nationals in Iraq or Syria who have chosen to fight for Islamic State make themselves "a legitimate target".
The Defence Secretary made the comments at a press conference following reports of the death of 'White Widow' Sally Jones, a notorious IS recruiter who is said to have been killed in a missile strike near the Iraq/Syria border.
Although he did not comment specifically on the case, Mr Fallon spoke generally about those who choose to fight for the terror group.
"You've made yourself a legitimate target," he said. "You run the risk every hour of every day of being on the wrong end of an RAF or a United States missile."
Mr Fallon also stressed that IS was preparing and inspiring terror attacks in the UK.
CIA chiefs reportedly confirmed to the UK government that Jones had been killed in June, according to The Sun, but it is understood the news was not made public over fears her 12-year-old son, Jojo, also died in the blast.
Sky's defence correspondent Alistair Bunkall said: "UK defence sources have told Sky News they believe the strike was successful but question some of the detail being reported in the media.
"The UK and US military has been working closely together on a number of high-profile targets in recent months and Jones is believed to have been on that list."
Jones became known as the White Widow after her British jihadist husband Junaid Hussain was killed in a US drone strike in August 2015.
Before fleeing to Syria, computer hacker Hussain admitted publishing Tony Blair's address in 2011 and was jailed for six months after making hoax calls to a UK counter-terror hotline a year later.
In an exclusive report in 2015, Sky News revealed the couple used online messaging services to urge British would-be recruits to carry out "lone wolf" attacks in the UK.
Following her husband's death, Jones was reportedly placed in charge of the female wing of IS' Anwar al-Awlaki batallion - a foreign fighter unit formed with the purpose of planning and executing attacks in the West.
The 50-year-old used her Twitter account to recruit women and shared pictures of herself with weapons.
Major General Chip Chapman, the former MoD head of counter terror, told Sky News Jones was a "significant" target for the US and UK.