| Country: | TUR |
| Type: | otoyol |
| Route: | 53 |
| Alternate Name: | Toprakkale-İskenderun Motorway Toprakkale-İskenderun Otoyolu |
| Terminus B: | İskenderun South |
| Length Km: | 150 |
| Regions: | Mediterranean |
| Provinces: | Adana, Hatay |
| Cities: | İskenderun |
| Map: | Karte O53 TR 2015.svg |
| Previous Type: | O |
| Previous Route: | 52 |
| Next Type: | O |
| Next Route: | 54 |
Otoyol 53 (English: Motorway 53), abbreviated as O-53, also known as Ceyhan-İskenderun Otoyolu (English: Ceyhan-İskenderun Motorway), is a toll motorway in Mediterranean Region, Turkey, connecting the Adana-Şanlıurfa Motorway O-52 with İskenderun. The motorway is part of international routes as European route E91 and Asian Highway 84.
The O-53 starts from Ceyhan in Adana Province at the junction of O-52, runs southward to İskenderun South bypassing the city in the east.