The siege of Nice occurred in 1543 and was part of the Italian War of 1542–46 in which Francis I and Suleiman the Magnificent collaborated as part of the Franco-Ottoman alliance against the Holy Roman Emperor Charles V, and Henry VIII of England. At that time, Nice was under the control of Charles III, Duke of Savoy, an ally of Charles V.

The siege was part of the 1543–1544 Mediterranean campaign of Hayreddin Barbarossa. A Franco-Ottoman army besieged Nice, breaching the walls and conquering sections of the city, but ultimately retired before taking the citadel due to the arrival of a Imperial-Savoyard relief fleet under Andrea Doria. Nice remained thus in Savoyard hands.

In the Mediterranean, active naval collaboration took place between France and the Ottoman Empire to fight against Spanish forces. Following an agreement between Francis I and Suleyman the Magnificent, through the intervention of the French ambassador in Constantinople, Antoine Escalin des Aimars, best known as Capitan Polin, a fleet of 110 galleys and 50 galiots under Hayreddin Barbarossa left from the Sea of Marmara in mid-May 1543. He then raided the coasts of Sicily and Southern Italy through the month of June, anchoring in front of Rome at the mouth of the Tiber on 29 June, while Polin wrote reassurances that attacks against Rome would not take place.

Barbarossa arrived with his fleet, accompanied by Polin, at Île Saint-Honorat on 5 July. As almost nothing had been prepared on the French side to assist the Ottoman fleet, Polin was dispatched to meet with Francis I at Marolles and ask him for support. Meanwhile, Barbarossa went to the harbour of Toulon on 10 July and then was received with honours at the harbour of Marseille on 21 July, where he joined the French forces under the Governor of Marseille, François of Bourbon, Count of Enghien. Barbarossa had originally intended to disembark in Spain, but it was prevented by their failure at besieging Perpignan and the presence of the imperial fleet under Andrea Doria in the gulf of Roses. Charles V had previously gathered 57 galleys and 40 carracks in Genoa for the occasion.

Franco-Ottoman attention turned towards the Duchy of Savoy, of which Nice was a part. Although Savoy had been a French protectorate for a century, Francis I chose to attack it because Charles III, Duke of Savoy had angered him by marrying Beatrice of Portugal, thus becoming an ally of the Habsburgs. Before Barbarossa's arrival, François de Bourbon had already attempted to make a surprise attack on Nice with ten galleys from Marseille, but had been repulsed by Doria coming with 44 galleys of his own, with four French vessels being captured. In order to besiege the city, Bourbon joined Barbarossa at Marseille in August 1543. Bourbon had reinforced his fleet with 26 galleys and 18 carracks with 7,000 soldiers. The combined fleet sailed out of Marseille on the 5th of August.

The Ottoman force first landed at Villefranche, 6 kilometers east of Nice, which it took and destroyed. The French and Ottoman forces then collaborated to attack the city of Nice on 6 August 1543.

The Franco-Ottomans were confronted by a stiff resistance which gave rise to the story of Catherine Ségurane, culminating with a major battle on 15 August, but the city surrendered on 22 August. The French prevented the Ottomans from sacking the city. They could not however take the castle, the "Château de Cimiez", apparently because the French were unable to supply sufficient gunpowder to their Ottoman allies. During the campaign, Barbarossa is known to have complained about the state of the French ships and the inappropriateness of their equipment and stores. He famously said "Are you seamen to fill your casks with wine rather than powder?".

Another important battle against the castle took place on 8 September, but the force finally retreated upon learning that an Imperial army was on the move to meet them: Duke Charles III, ruler of the Duchy of Savoy, had raised an army in Piedmont to free the city.