Speeding transport truck lost control and crashed into homes, killing 13 villagers and the driver.
The driver was speeding around a bend when he lost control and careered into the small village of Cambesse, 180km (120 miles) south of the capital Bissau.
A hospital worker in Bissau confirmed the death toll.
Guinea-Bissau is an impoverished former Portuguese colony of about two million people, where the state of roads is poor and accidents are frequent.
The road south of the capital is often busy during the spring harvest of cashew nuts, the country’s main export.