Nick Kyrgios of Australia ended Daniil Medvedev's defence of the US Open title after winning four-set in New York.
The 27-year-old Australian demonstrated all of his shot-making and propensity for creating drama in a 7-6 3-6 6-3 6-2 win in the last 16.
Medvedev will lose his ranking as world number one after the defeat.
Kyrgios will face Karen Kha-cha-nov in the quarter-finals.
Khachanov reached his third Grand Slam quarter-final by outlasting Pablo Carreno Busta in a 4-6 6-3 6-1 4-6 6-3 win.
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