Tensions over the sea -- which China claims almost entirely -- have spiked as Beijing refuses to pull out vessels from the Philippines' Exclusive Economic Zone and Manila steps up maritime patrols.
Duterte is under growing domestic pressure to take a harder line, but has been reluctant to confront China over the issue as he fosters closer ties with the economic giant.
He said late Wednesday (April 28) that while the Philippines is indebted to its "good friend" China for many things, including free Covid-19 vaccines, his country's claims to the waterway "cannot be bargainable".
"I'll tell China, we do not want trouble, we do not want war. But if you tell us to leave -- no," Duterte said.
"There are things which are not really subject to a compromise, such as us pulling back. It's difficult. I hope they understand, but I have the interest of my country also to protect."
Duterte's remarks came after the country's defence department said "China has no business telling the Philippines what we can and cannot do with our own waters".
The Philippine coast guard is conducting drills near Thitu Island and Scarborough Shoal, as well as the Batanes islands in the north and the southern and eastern parts of the country.
Scarborough -- one of the region's richest fishing grounds -- has long been a flashpoint between Manila and Beijing.
In response to the exercises, China's foreign ministry said Monday the Philippines should "stop actions complicating the situation and escalating disputes".
In recent weeks, Manila has boosted "sovereignty patrols" involving the navy, coast guard and fisheries in the Spratly Islands -- an archipelago contested by several countries.
Beijing has ignored a 2016 international tribunal decision that declared its historical claim over most of the South China Sea to be without basis.
Once-frosty ties between Manila and Beijing have warmed under Duterte, who set aside the ruling in exchange for promises of trade and investment -- which critics say have not materialised.
Delays in Covid-19 vaccine deliveries has left the Philippines heavily reliant on the CoronaVac jab developed by China's Sinovac.
Around 3.5 million doses of CoronaVac have been sent to the Southeast Asian country so far, including one million donated doses. - AFP