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[caption id="attachment_21220" align="alignnone" width="580"] Djokovic, Nadal match-up looms at US Open. Twitter[/caption] Internet Desk: Novak Djokovic could have a tricky start to defending his US Open championship, and it won't get any easier later for the Serbian in New York, where main draw play starts on Monday. The top seed and two-time champion (2011, 2015) will open against former World No. 14 and 2013 Wimbledon semi-finalist Jerzy Janowicz. In the second round, Djokovic could face one of the five players to gain a win against him this season: Czech Jiri Vesely, who beat Djokovic in the second round at theMonte-Carlo Rolex Masters in April. From there, the Belgrade native could meet 28^th seed Martin Klizan for the third time. Djokovic beat the Slovakian twice on hard courts last season. If the seeds maintain, Frenchman Richard Gasquet, 13^th seed, or 20^th seed John Isner could challenge the Serbian in the fourth round. Croatian Marin Cilic, 2014 US Open champion, could meet Djokovic in the quarter-finals. Seventh seed Cilic heads to New York playing some of his best tennis since he captured his first Grand Slam championship two years ago. The 6'6” right-hander beat Andy Murray last week in Cincinnati to take his first ATP World Tour Masters 1000 title. In the semi-finals, fans could see the 50^th installment of Djokovic v. Rafael Nadal. The 29-year-old right-hander has won their past seven encounters. Fourth seed Nadal debuts against Uzbekistan's Denis Istomin and could face Frenchman Stephane Robert or Italian Andreas Seppi in the second round. The Spaniard's first seeded opponent could be countryman Albert Ramos-Vinolas, the 31^st seed, in the third round. Another Spaniard Roberto Bautista Agut, the 15^th seed, or 24^th seed Lucas Pouille of France might meet Nadal in the fourth round. Tenth seed Gael Monfils or fifth seed Milos Raonic could battle Nadal in the last eight. Both Monfils and Raonic open against hard-charging, big servers: Monfils plays Luxembourg's Gilles Muller; Raonic plays Germany's Dustin Brown. On the other half of the draw, second seed Andy Murray, 2012 US Open champion, opens against the Czech Lukas Rosol and could meet Spaniard Marcel Granollers or Argentine Juan Monaco in the second round. Awaiting Murray in the semi-finals could be third seed Stan Wawrinka, but the Swiss will have to fight past a difficult early stretch. He opens against World No. 47 Fernando Verdasco, who beat Wawrinka on grass at the Aegon Championships in June. Juan Martin del Potro, 2009 US Open champion, returns to New York by wild card and debuts against fellow Argentine Diego Schwartzman. Del Potro could meet 19^th seed and top American Steve Johnson in the second round. Spanish veteran David Ferrer, the 11^th seed, could await in the third round before del Potro might face Thiem in the Round of 16.