Mississippi Highway 345 (MS 345) is a 9.272-mile-long (14.922 km) north–south state highway in Pontotoc County, Mississippi, connecting the city of Pontotoc with the town of Ecru.

MS 345 begins in the city of Pontotoc at an intersection with MS 9 (North Main Street) at the northern edge of downtown.

It heads north, along North Main Street, through neighborhoods for two miles (3.2 km) to an intersection with U.S. Route 278 (US 278)/MS 6 (Pontotoc Parkway), where it leaves Pontotoc.

The highway winds its way through a mix of farmland and wooded hills for the next several miles, where it crosses Cherry Creek (one of two creeks forming the Little Tallahatchie River) before passing through the community of Cherry Creek, where it makes a sharp left turn.

MS 345 now enters the town of Ecru along Main Street and passes through neighborhoods, then straight through downtown before coming to an end at an intersection with MS 15.