At the 2006 and 2007 parliamentary elections, Klyuyev was re-elected as a deputy for Party of Regions. On March 11, 2010 Klyuyev was appointed the First Vice-Prime Minister in the Azarov Government, and after the Yanukovych administrative reform on December 9, 2010 he also has accepted the assignment of the Minister of Economic Development and Trade. On February 14, 2012, Klyuyev was appointed Secretary of the National Security and Defense Council of Ukraine (NSDC). Insiders in the Party of Regions always claimed that his removal from the post of the First Vice Prime Minister, responsible for the European Integration of Ukraine, happened due to the personal conflict with the Head of the Presidential Administration, Sergiy Lyovochkin and was to be seen as a punishment for his influential position within the institutions of the European Union. This shift placed Klyuyev, as the chief campaign manager of the Party of Regions, in the position to ensure that the Party of Regions would win the elections in the fall of 2012. NSDC secretary sees Azarov as likely candidate for premiership. On 24 January 2014, President Yanukovych signed a decrees that dismissed Klyuyev as National Security and Defense Council secretary and appointed him head of the Presidential Administration of Ukraine. On 23 February 2014, just after the "Maidan revolution", Klyuyev resigned from this post. His spokesman, Artem Petrenko, claimed 2 days later that Klyuyev's had been wounded when his car had been attacked while he was travelling back to Kiev from Crimea after tendering his resignation to former President Yanukovych. Since 7 March 2014 he is wanted for involvement in mass murder. The day before the EU froze his assets. In June 2019 the Central Election Commission of Ukraine refused Klyuyev to register for the 21 July 2019 Ukrainian parliamentary election is a candidate for the Liberal Party of Ukraine in Electoral District 46 situated in Donetsk Oblast because he had not lived in Ukraine for 5 years. The Supreme Court ordered the Central Election Commission on 1 July 2019 to reexamine Klyuyev's application and his claim that he had lived in Donetsk the last 5 year and that since Donetsk is Ukrainian territory he lived in Ukraine the last 5 years (although Donetsk is not controlled by Ukrainian authorities since the start of the War in Donbas in 2014). The same day the Central Election Commission registered Klyuyev's candidacy. Eventually Klyuyev was not able to take part in the election as his registration was cancelled and constituency 46 was won by Opposition Platform — For Life candidate Fyodor Khristenko (who won with 38,01% of the votes).