Their last meeting was in the 2017 Australian Open final, where Serena beat her sister in straight sets while several weeks pregnant. "In a game I loved with all my heart, at one of my most cherished tournaments, I suddenly felt unwelcome, alone and afraid".
This is the first time the siblings will play each other at the BNP Paribas Open. She marked the occasion with a gold-toned "S" Serena pin that was available to fans who came to see her play.
After her second round win over Kiki Bertens, Serena said she "would prefer to play someone else, anybody else, literally anybody else, but it has to happen now".
The 36-year-old will battle against her older sister Venus on Monday night for a spot in the fourth round.
After the 2001 Indian Wells showpiece, Serena boycotted the tournament for 13 years.
In the men's section, Spanish veteran Fernando Verdasco used his powerful serve to upset third seed Grigor Dimitrov 7-6 (4) 4-6 6-3 while Roger Federer's tournament debut was hampered by rain.
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Venus did her part to set up the marquee match when she dismantled World No.35 Sorana Cirstea 6-3, 6-4 in just 79 minutes.
"That's, you know, totally gone out of my mind", she said.
"It's a huge difference to play her in the semi-finals or even the quarter-finals or a final as opposed to the third round".
The crowd's treatment led to a 14-year boycott by the sisters, which Serena finally ended in 2015. "We can always stay in the tournament longer if the both of us are in the tournament". She said their father, Richard, would probably decide - an insinuation that their matches were rigged. Venus enjoyed a resurgent 2017 season, but she began this year with losses to Angelique Kerber in Syndey and Belinda Bencic at the Australian Open. In fact, it's the first time they've met before the Round of 16 since their very first head-to-head matchup more than 20 years ago.
Talking about competing in the upcoming Grand Slams tournament, Serena was quoted as saying, "If I want to play in those grand slams and play well then now is the flawless time to start".
Venus' last defeat of her younger sister was at the Canadian Open in 2014, where she prevailed in a three-set semi-final.