The 20-year-old's stunning dismantling of the Russian was a far cry from their epic five-setter that lasted nearly five hours in the second round at Melbourne Park last year, with Tien wrapping up the contest in an hour and 42 minutes on Margaret Court Arena.
Drama struck early when Tien took a medical timeout just 10 minutes into the fourth-round encounter as he stuffed tissues up his nose, but that did little to stop his dominance on court as he left Medvedev looking utterly lost on numerous rallies.
Medvedev had said he did not like playing Tien after a trilogy of matches that went the distance last year and the 20-year-old American proved him right with a clinical performance that included 33 winners.
The victory made Tien the youngest quarter-finalist at the Australian Open since Nick Kyrgios in 2015 and he will next play third seed Alexander Zverev, who crushed Francisco Cerundolo 6-2 6-4 6-4.
"It feels amazing. It's so special to do it, especially here, where it's always so special for me to come back and play every year," Tien said.
"This is a big goal for me this year and I'm just super happy ... every year it's been so special to come back and play in front of a crowd like this with this much energy and support."
Fast start
After making a fast start by breaking Medvedev in the opening game and consolidating the break before the nosebleed, Tien showed no signs of slowing down following eight minutes of treatment.
He went toe-to-toe with the Russian, who has historically struggled against left-handed players at Grand Slams.
The American calmly held serve and took the opening set with a glorious forehand winner down the line that left Medvedev muttering to himself during the changeover.
Whatever he told himself, it did little to improve his chances as Tien consolidated a double break to move 4-0 up in the second set as Medvedev angrily asked his coaching team what he could do to stop the rot.
He had no answers as Tien covered all corners of the court to fire winners, while he was emphatic at the net when Medvedev attempted the serve-and-volley as his young opponent went 5-0 up.
Tien Bagles Medvedev
Tien then went two sets up with another statement backhand winner after playing calculated shots to draw Medvedev to the net, as the Russian lost a set 6-0 for the first time in Grand Slams.
It was deja vu in the third set too as Tien employed the drop shot to good effect to go 3-0 up in 11 minutes as Medvedev found no way through the American who covered the court with ease.
Medvedev finally found his range when he earned his first break point and converted it to make it 4-2 while unforced errors began to creep in for Tien.
However, he held his nerve to knock out the three-times finalist and hand him his first defeat of the year.