Brown said the 10 countries in the Association of Southeast Asian Nations, or ASEAN, have distinct political and economic views on China, but they share a wariness about its territorial claims. He said Clinton is likely to capitalize on these concerns.

"I think it's really kind of setting out a framework where, in fact, it's not just about China's interest, and China's going to have to start factoring in the fact that it's going to get a lot of opposition if it's just going to be unilaterally declaring its interests and think that the ASEAN countries are going to lie down," said Brown.

Clinton's trip will be her sixth to Asia in 18 months, reflecting the Obama administration's effort to sharpen its focus on the region that had been overshadowed by the wars in Iraq and Afghanistan.

U.S. focuses on region, China

David Lampton of the School of Advanced International Studies at Johns Hopkins University in Washington said U.S. efforts to warm up to its Asian allies is unsettling to China.

"Of course, China plays a major role in the region and tends to have a kind of lens or framework of containment. And so as the U.S. is trying to improve relations, I think this raises alarm bells in Beijing, seeing this as some kind of effort to contain China," said Lampton.

Despite ongoing tensions between Washington and Beijing over regional security, currency issues and human rights, Clinton added a brief visit to China's Hainan Island to her agenda just days before her departure.