The Titans had looked set for a swift victory when they set a massive target of 549 and then reduced the Knights to 42/3 shortly after tea on the third day.
However, Second and Van Biljon dug in for the remainder of the session to go to stumps unbeaten on 76 and 73 respectively as the Knights reached 180/3.
The Titans declaration was set up by their overnight batsmen, Farhaan Behardien and Roelof van der Merwe, who went on to score 83 and 121 respectively.
Van der Merwe now has two centuries - one of them a double - and a fifty in the Sunfoil Series, making him the leading run-scorer in the competition with 417 from three matches.
Thanks to him and Behardien, the Titans total moved along from 115 for three at the start of the day to 367/7, with captain Behardien declaring the innings once David Wiese had reached a 48-ball 50.
All of the Knights bowlers came in for some tap in the Titans’ second innings, as the visitors scored at 4.28 runs per over, but Obus Pienaar’s 2-53 were the most respectable figures.
Rowan Richards had done the damage as the Knights were bowled out for 185 in their first dig, and he struck again at the start of the second as he had Reeza Hendricks and Gihahn Cloete caught behind by Mangaliso Mosehle.
With Marchant de Lange inflicting the same fate on Gerhardt Abrahams, who grabbed a pair for the match, the table-topping Knights appeared set for their first defeat of the campaign.
The Titans will still fancy their chances of inflicting it on the final day, but will first need to dislodge Second and Van Biljon.