Rafael Nadal's comeback tournament at the Brisbane International ended in the quarter-finals as home favourite Jordan Thompson prevailed in an enthralling three-set battle.

The 22-time major winner was made to pay for missing three match points in the second set as Thompson came from behind to record a 5-7 7-6[6] 6-3 victory in three hours and 26 minutes.

Thompson hit a total of 44 winners throughout the contest - 12 more than his revered foe - while also committing just 14 unforced errors in an exceptional display, which also marked his maiden win over Nadal on the ATP Tour.

The Spaniard had triumphed in their first two meetings at the 2020 Paris Masters and 2022 French Open, although he was briefly on the back foot against Thompson, who earned the first break in the seventh game of the match.

However, Nadal fought back straight away and capitalised on a error-strewn service game from his Australian foe in the 12th game, breaking again to 15 to take the opener and putting pressure on Thompson's serve straight away in the second.

Thompson crucially saved three break points to hold for 2-2, but a trio of successive unforced errors handed Nadal his first opportunity to clinch a two-set win in the 10th game, which he squandered with a backhand volley into the net.

The 37-year-old attempted to consign that missed chance to history as he raced into a 3-0 tie-breaker lead before fashioning another two match points at 6-4, but Thompson miraculously saved both of them and forced the unlikeliest of third sets with a forehand smash right onto the baseline.

A fatigued Nadal had no answer to Thompson's remarkable grit in the decider, as the home favourite won four of the first five games before earning his first match point on another unforced error from Nadal.

During a phenomenal 33-shot rally - the longest point of the match - both players kept their focus despite the unwelcome distraction of two train horns, and Nadal eventually overcooked a backhand to send Thompson through to the semi-finals.

"That was something special. I think that train needed some WD-40 the whole match! I completely forgot I saved match points, but to beat Rafa at home, I think it's my first semi-final on hard court so couldn't be happier," the world number 55 said on the court.

Thompson will now square off with Bulgarian second seed Grigor Dimitrov for a spot in the Brisbane final, where either top seed Holger Rune or Roman Safiullin will await the victor.