More than 2,000 people have signed an online petition calling on the prime minister to write off the Humber Bridge debt and reduce tolls.
More than six million vehicles cross the bridge every year
The petition, on the Downing Street website, said it is time the £320m debt was wiped out and tolls reviewed in a bid to reduce them.
In April last year, the charges for car drivers were increased by 20p to £2.70.
The petition was posted by Paul Harrop, who said the charges created hardship and held the region back economically.
Mr Harrop said the Humber Bridge had the highest toll charges in Britain.
"This not only creates hardship for individual, particularly those who have no choice but to use the bridge for commuting and hospital visits, it also holds the Humber region back economically," he said.
"Much of the current tolls are used to pay back the artificially high government loans provided over 25 years ago to build the bridge.
"The government has the power to write off this debt. This would enable the bridge board to keep tolls at a fair level."
Another petition on the website, signed by 136 people so far, calls on Tony Blair to scrap tolls for people who need to go over the bridge for medical treatment.
Once the petitions have closed, they will be passed on to the relevant government department for a response, which will be e-mailed to every person who signs the petitions.