Borisenko served as a flight engineer on board Soyuz TMA-21 for Expedition 27, the 27th long-duration mission to the International Space Station (ISS).

[5] After 2 days of autonomous flight, the Soyuz TMA-21 spacecraft docked with the International Space Station (ISS) on April 6 at 23:09 UTC, with the crew officially joining the crew of Expedition 27, alongside Russian commander Dmitri Kondratyev, NASA astronaut Catherine Coleman and Italian astronaut Paolo Nespoli.

[8] Borisenko concluded his stay aboard the ISS, when his spaceship, Soyuz TMA-21 undocked from the Russian segment's Poisk module at 00:38 UTC on September 16,.

[9] On the same day, the Soyuz TMA-21 capsule carrying Borisenko and his two crew mates, Alexander Samokutyaev and Ron Garan touched down (3:59:39 UTC) at 93 miles southeast of the city of Zhezkazgan in Kazakhstan.

On the ground, Borisenko appeared to be in good spirits as he flashed up an enthusiastic "thumbs-up" signal shortly after he was pulled out of the Soyuz landing capsule.

After attending the traditional greeting ceremony at the airport in Karaganda, Kazakhstan, Borisenko boarded a plane to return to the training base in Star City, Russia.

[12] Borisenko and his two crew mates, Roscosmos cosmonaut Sergey Ryzhikov and NASA astronaut Shane Kimbrough rendezvoused and docked to the ISS on the 21st of October following a two-day rendezvous, and officially joined the Expedition 49 alongside Russian commander Anatoly Ivanishin and flight engineers Takuya Onishi of JAXA and Kathleen Rubins of NASA.

The trio safely landed on the Kazakh Steppe less than five hours later, wrapping up a 173-day spaceflight and bringing Borisenko's total time in space to 337 days.