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|Major roads:||O-52, O-54|
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It's not very hard to find rides with truckers from Istanbul to Gaziantep, you just have to find the right spot.
harveypekar told his ride into the city he was coming only for the baklava, and was treated to a heroic quantity as well as being dropped off back on the highway.
Gaziantep is a surprisingly large city with almost 2,000,000 inhabitants, so unless you intend to stay/sightsee for a while in the city, try to get a lift that will take you further from the city when crossing west to east (i.e. Osmaniye to Urfa) and vice versa as it is likely a very long walk to the edge of the city from downtown. If you happen to cross the city west to east, keep in mind that Nizip is a good place about 40 km east of Gaziantep to get a lift to Urfa.
guaka did it in 2008 but doesn't remember much of the details. Maybe he even took a bus to Kilis. It looks like you have to go towards the airport. There's not much traffic south from Kilis (on the Gaziantep Kilis Yolu), so it's probably better to first get into the center of Kilis and then go South from there if you're heading to Syria.
East towards Urfa, Mardin, Diyarbakir
From the city centre you can take the tram which costs around 2TL to the east end of the tracks to the "Gar" (train station). From here, you're a 5-10 minute walk to the D400 highway that goes through the city. You can see it from the Gar. Once you get to the highway you can hitch a ride out of the city to where the D400 continues on to Urfa, or leave your ride when the D400 comes close to the O52 toll highway and you can walk to that and take a ride from there. User:ballenuk hitched from the O52 just at the edge of the city where it comes within a few hundred metres of the D400 in March 2017. A car stopped within two minutes and went right to central Urfa.