The trailer broke open and spilled out migrants when the truck crashed on a sharp curve outside the city of Tuxtla Gutierrez in the state of Chiapas, according to video footage of the aftermath and civil protection authorities.
The Attorney General's office put the death toll at 53.
"It took a bend, and because of the weight of us people inside, we all went with it," said a shocked-looking Guatemalan man sitting at the scene in footage broadcast on social media.
"The trailer couldn't handle the weight of people."
Several dozen people were injured and taken to hospitals in Chiapas, which borders Guatemala. More than 100 people were traveling inside the trailer, authorities said.
A Reuters witness heard cries and sobs among survivors as emergency personnel rushed to their aid.
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