Djokovic posts routine win on return to action in Tel Aviv
Djokovic had not featured in an ATP-level match since his final victory over Nick Kyrgios at Wimbledon, having been forced to miss the US Open due to his COVID-19 vaccination status.
But the Serbian needed little time to find his feet in Israel, winning the first seven games of the match and breaking the Spaniard's serve four times en route to a 6-0 6-3 victory.
Speaking on court afterwards, Djokovic said: "Fantastic atmosphere here tonight, thank you very much. I like the court, it's very intimate and it's very loud.
"The crowd here is very passionate about the sport, about tennis and I'm really, really happy to be here and to perform here in front of you, so thank you for your support."
The 21-time grand slam winner will face Canada's Vasek Pospisil in the last eight after he beat home hopeful Edan Leshem 6-3 6-2.
Two of Djokovic's fellow seeds fared less well, however, with Diego Schwartzman and Botic van de Zandschulp both being ousted after three-set contests.
Third seed Schwartzman failed to capitalise on a third-set match point in his 6-3 2-6 7-6 (9-7) loss to Arthur Rinderknech, while Britain's Liam Broady teed up a clash with Marin Cilic by beating Van de Zandschulp 6-4 4-6 6-3.
The Sofia Open also saw a couple of seeds fall to surprise defeats on Thursday, although Jannik Sinner avoided any drama in his 6-3 6-4 win over Nuno Borges.
Sinner now has a perfect 10-0 record at the event, which he won in both 2020 and 2021, and will face Australia's Aleksandar Vukic for a place in the final four.
Holger Rune also progressed to the last eight, though he was forced to rally after losing the opener against Lorenzo Sonego, but Pablo Carreno Busta and Oscar Otte were both dumped out.
Second seed Carreno Busta fell to a 6-3 3-6 6-2 reverse against Switzerland's Marc-Andrea Huesler, who will face Poland's Kamil Majchrzak in the quarter-finals after he came back to beat Otte 4-6 6-2 6-4.