The 2018 champion compiled a hat-trick of century breaks but opponent Liang Wenbo still forced what proved to be a dramatic final frame.
O’Sullivan, not for the first time against Liang, held his nerve at the crucial moments to advance to the quarter-finals at the Centaur.
The “Rocket” is making his first appearance in a tournament this year after opting out of the Masters in January.
Graeme Dott represents O’Sullivan’s upcoming challenge after the in-form Scot progressed in contrasting fashion.
Dott has carried forward the form that saw him reach the semi-finals of last week’s German Masters, and the 42 year-old ran out a comfortable 4-0 winner against Xiao Guodong on day three this week.
English duo Gary Wilson and Tom Ford are also through to the last eight after respective triumphs over Matthews Stevens and Selt.
Ford’s clash with Selt was billed as a grudge match after an ill-tempered Championship League battle in January ended with the latter refusing to shake Ford’s hand.
Meanwhile, the first round also concluded with legends John Higgins and Mark Williams among those remaining in contention.
There was a significant amount of attention surrounding the Welshman’s tie with Barry Hawkins, given how Williams had been suffering with gout in the run-up to this week’s action.
The three-time world champion sported special footwear and managed his discomfort to still eke out a 4-2 defeat of 2017 World Grand Prix champion Barry Hawkins.
Higgins recorded the same scoreline against recent Masters champion Stuart Bingham, with Kyren Wilson and Zhao Xintong edging through as well.
That quartet will be involved in Thursday’s afternoon session as the last 16 is played to a climax, before the quarter-finals begin later in the evening.
The World Grand Prix is the first of three events in the Coral Series, with additional tournaments to follow in Southport and Llandudno.
The player who performs the best across the series will earn a £100,000 bonus.