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Gagarina was born in Moscow, Russian SFSR, USSR but spent most of her youth in Greece. Her mother was a ballet dancer. In 1993, Gagarina's father died and her mother decided to move the family back to Russia. However, they soon moved back to Greece and settled in Athens. After completing her education, she moved to Saratov to live with her grandmother.
In 2003, Gagarina competed in season two of Star Factory, a Russian reality singing competition. She performed several songs by Maxim Fadeev and went on to win the show, but refused to work with Fadeev after her victory. After winning Star Factory, Gagarina was invited to perform in the group Playgirls. The group received a recording contract with ARS Records, but ultimately disbanded. In 2005, she performed at the New Wave competition held in Jūrmala, Latvia and placed third. She later released the singles "Kolybelnaya", "Morning", "Ya tvoya", "Pomnyu", and "Ya tebya ne proshchu nikogda". Her début album Попроси у облаков was released in 2007.
In 2008, Gagarina released the single "Komu, zachem?" with Russian singer Irina Dubtsova. In March 2010, her second studio album О себе was released. In 2012, Gagarina starts to collaborate with Konstantin Meladze, Russian/Georgian producer, well known for his successful project "VIA GRA". With Meladze she recorded four singles: "Spektakl okonchen" ("The Play Is Over") RUS #10, UKR #3, "Net" ("No") RUS #3 UKR #1, "Navek" ("Forever") RUS #26, UKR #23 and "Shagay" ("Stride") RUS #15, UKR #11.
On 9 March 2015, it was revealed that Gagarina would represent Russia in the Eurovision Song Contest 2015. Gagarina placed second in the Grand Final of Eurovision Song Contest 2015 with the song "A Million Voices". On July 25, 2015 she performed the closing song of the "FIFA World Cup - Russia 2018" drawing show in St. Petersburg, shown on television worldwide.
On 25 August 2007, she married Russian actor Pyotr Kislov. She gave birth to their son, Andrey on 14 October 2007. They divorced on 31 March 2010. She married photographer Dmitry Iskhakov on 9 September 2014.