Tottenham's current three-match winning streak means they are favourites in what will be Defoe's 15th appearance in a north London derby.
The England hitman's partnership with Emmanuel Adebayor, who is set to receive a hostile reception from the Arsenal supporters, has been key to Tottenham's upturn in form, with the pair finding the net seven times since Adebayor signed on loan from Manchester City for the season.
The pair combined well in last week's 2-1 win over Wigan and they both got on the scoresheet in Spurs' highly-impressive 4-0 hammering of Liverpool - a team regarded as one of their main rivals for a top-four position.
Defoe is happy that he and his team-mates have hit form going in the match, and is sure that Spurs will win if they play to the best of their ability.
"It's the big one, a massive game," Defoe said.
"Games like these are the ones you want to play in. I will definitely be ready for it. I'm sure the fans can't wait and we can't either.
"With the way that we are playing, we are confident. If we play like we did against Liverpool, with the same intensity, the same passing and the same movement that we did against them, then I can't see why we can't win the game."
Defoe missed last week's win at the DW Stadium due to illness but looked sharp on Thursday when he scored one and set up another in Spurs' 3-1 Europa League win over Shamrock Rovers.
The 28-year-old, who scored just four league goals last season, is happy to have hit the ground running this term and is confident of scoring what would be just his second north London derby goal this weekend.
"I was disappointed to miss the Wigan game through illness so I'm glad I had a good run out on Thursday," he said.
"I was happy to score again. I have always said that once I get back in to the habit of scoring I'll feel like I can score in every game."
Having spent all his career at Tottenham, no-one in Harry Redknapp's squad knows more about north London derbies than club captain Ledley King.
After years of being underdogs in the contests, Spurs have enjoyed relative success in the fixture in recent years, losing just two north London derbies since Redknapp took over - one of which was in the Carling Cup.
Redknapp's team also took credit for beating Arsenal away for the first time in 17 years last season.
King was absent that day through injury, but was happy to see his team-mates continue their recent good form in the fixture.
"I was delighted for the lads last year. They showed great spirit to come back from 2-0 down and win 3-2," the defender said.
"We looked in for a beating at 2-0 down but the lads showed great courage and determination and I was delighted to see Younes (Kaboul) score the winner.
"In recent years it has been a lot tighter than it was.
"For many years we struggled against them but it has evened its self out in the last few years and we have been on top so let's hope that continues."
King thinks that the vast experience within the Tottenham squad means they will be able to cope better with the raucous atmosphere expected at White Hart Lane this weekend.
"They're always massive games against Arsenal," King added.
"There won't be too many lads who haven't experienced the derby before, maybe just Scotty Parker at the moment.
"He is an experienced player though and he'll know what it's all about.
"The rest of us know it's a great game to be involved in.
"When you drive up to the ground it's a completely different feeling and when you get out playing the atmosphere is electric."