Borrell told reporters "It's an issue of life and death for many human beings. And the question is that Russia has to de-block and allow Ukrainian grain to be exported."
"The most worrisome thing is the lack of food in many countries around the world, and there is not food because Russia is blocking the export of Ukrainian grain," Borrell said.
Borrell spoke as he arrived at a meeting in Brussels of EU foreign ministers to discuss closing loopholes in their sanctions regime to punish Russia for the invasion.
He said that Ukraine's European allies would do what they can to help Kyiv export its grain through overland routes and across the Danube river, but warned that the ports were key.
"The life of thousands -- more than thousands -- tens of thousands of people depends on this agreement. So it's not a diplomatic game."
Russian and Ukrainian negotiators will meet UN and Turkish diplomats in Istanbul on Wednesday to discuss a possible agreement to end the months-long blockade of Ukraine's ports.
A Russian foreign ministry spokesman has stressed that Moscow would attend the meeting with a list of firm demands -- including the right to search grain ships for weapons.
Ukraine has its own list of demands for security guarantees and has stressed the importance of the UN's role in brokering the talks.
NATO member Turkey -- on speaking terms with both Russia and Ukraine -- has spearheaded efforts to resume the grain deliveries.
But Germany's agriculture minister Cem Ozdemir did not share Borrell's guarded optimism that the talks would bear fruit and reopen Black Sea shipping.
"I don't believe the Black Sea will be safe again for Ukraine as long as Vladimir Putin or a comparable criminal in Moscow is in charge. Brussels must look for a permanent alternative route."
Borrell said that if Wednesday's UN talks failed, Brussels would continue to blame Russia for using the threat of starvation as "a weapon" in its conflict.