The Sierra de Santa Cruz is a small mountain range in eastern Guatemala. It is situated north of Lake Izabal, in the department of Izabal. The mountain range has a south-west to north-east orientation, and is approximately 55 km long and 13 km wide. Its highest peaks have an altitude of approximately 1100 m ().
Craugastor trachydermus, a species of frog in the family Craugastoridae, is endemic to Guatemala and only known from its type locality, Xiacam in the Sierra de Santa Cruz. It is critically endangered.