The Paraguayan international has barely featured for Premier League champions since joining for £17 million from Blackburn Rovers in 2009 and has taking in loan spells at Ewood Park and Real Betis in the last two years.
Roberto Mancini has been tasked by the clubs hierarchy with trimming his squad and Santa Cruz will be one of the first he will look to offload from the Etihad Stadium.
The 30-year-old has returned to England for pre-season training and Hughes is said to be interested in signing him for a third time having done so at Blackburn and City.
Santa Cruz hinted that a switch to Loftus Road would appeal to him also professing his admiration for the R’s chief following their spells working together.
“Everybody knows that I have big respect for him and will always be very thankful to him for the time we worked together,” Santa Cruz told Sky Sports News HD.
“I hope that he will have a great season and achieve his goals. Who knows? I want to play, I want to do good and I want to be successful. Who knows, we might work back together.
“I haven’t spoken to him or anybody so it might be a long way to happen, but the important thing for me is to be fit and try to go to a place where I will play.”
Hughes is also though to be closing in on the signing of free agent Junior Hoilett after he agreed terms on a move to West London following his release from Blackburn.
He would become Rangers’ fifth summer signing following Samba Diakite, Samba, Andy Johnson, Park Ji Sung, Rob Green and Ryan Nelsen.