McCain noted politicians in Mexico have been targeted by the cartels that are smuggling drugs into the United States and that hundreds of illegal immigrants die in the desert every year trying to sneak into the country.
"The brutality and the human rights abuses are beyond horrendous," McCain said.
Democratic challenger Rodney Glassman believes the government must find a way for foreign workers to come into the country legally. He criticized the four-term senator's emphasis on securing the border before first confronting the economic realities that motivate people to come into the country illegally.
"It's about having someone who is going to work with everyone to find solutions, not just serve as a partisan battering ram trying to accomplish nothing except self-aggrandizement and furthering their political future," said Glassman, a former Tucson city councilman.
Illegal immigration and drug violence in Mexico took center stage during the one-hour, televised debate.
McCain, who once championed a path to citizenship for the nation's estimated 12 million illegal immigrants, didn't respond directly to Glassman's criticism and instead stuck to his message of border security.
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"If we don't secure the borders first, we will find ourselves with another group of people who have come to this country illegally and then we will have to deal with it all over again," McCain said, adding that guest-worker programs can be considered after the border is strengthened.
Glassman said Arizona - the busiest illegal entry spot into the United States - receives less than its fair share of resources to secure the border and speed up legitimate commerce with Mexico.
"We have not had a champion for securing our border and promoting commerce," Glassman said.
McCain said Arizona's borders can be secured with more border agents, more border fencing and more surveillance.
"We have made progress in San Diego and in some other places," McCain said. "We have made progress in Yuma. We need to do the same thing in Tucson."
Green Party candidate Jerry Joslyn said building more fences along the border won't do the trick because nearly half of the illegal immigrants in the United States came here legally and then overstayed their visas.
Libertarian candidate David Nolan said the most effective way to end border violence and cripple Mexico's drug cartels is to decriminalize drugs.