Sunderland take on Newcastle United this weekend.
The England international is not new to derby clashes, having featured in big games for West Ham United as well as the North London duel between Premier League title chasers Arsenal and Tottenham Hotspur.
But upon joining Sunderland last season, Defoe was informed by teammate Cattermole of the significance of the Tyne-Wear derby as he explains how the midfielder sees it as the biggest encounter in England.
When I signed, I spoke to Lee Cattermole, who said to me, ‘I know that Tottenham-Arsenal games are big, but this is the one’, Defoe shared with Alan Shearer for The Sun.
“I remember getting up in the morning of the game last year, and it felt like Cup final day. We went for a walk and there were fans outside the hotel, and normally it’s not like that.
"Seeing all the little kids coming up to me and saying, ‘Good luck’ — it was so important for the fans. Driving to the stadium, all the pubs were packed. That’s when I thought, ‘This is big’.”
Defoe netted the winner between the two sides at the Stadium of Light last season, a result which helped the Black Cats edge towards safety under then-boss Dick Advocaat.
Fast forward 12 months and Sunderland find themselves in a similar position, 18th in the Premier League table and in search of a vital three points in their quest to survive.
The difference this time around, though, is that Newcastle are in a similar boat as the Magpies sit in 19th position in the table, one point behind Sunderland and four adrift of Norwich City and safety.
The stakes for this Tyne-Wear derby could not be any bigger, with many predicting that a defeat for either side will prove catastrophic in their bid to preserve their Premier League status come May.