The 18-year-old striker, signed on a month's loan from Southampton after Steve MacLean broke a leg in a pre-season friendly, pounced after just eight minutes.
But his injury leaves the worried Hillsborough manager with only two strikers and he could be forced to sign another frontman on loan before the transfer window closes.
Peter Taylor's Hull side played their part in a Hillsborough thriller in front of a bumper 30,000 crowd but blew a string of chances.
Veteran frontman Nick Barmby levelled matters in the 23rd minute rounding off a sweet three-man move with a cool finish.
But Wednesday had to produce two goalline clearances as Hull threatened to grab the points.
Midfielder Glenn Whelan carved out the Wednesday opener with a clever cross from the right finished off in style by Best with his first ever league goal.
Barmby hit back 15 minutes later but then Taylor watched in agony as Hull were denied by two clearances and a glaring miss by Stuart Elliott.
Ian Ashbee headed into the path of Craig Fagan who volleyed into the path of the form Spurs, Liverpool and Everton star.
Leon Cort came close to heading Hull in front but American defender Frankie Simek blocked on the line.
Hull almost romped into the lead after 58 minutes in a bizarre goalmouth incident. Jason Price skipped around David Lucas who was left stranded as he shot but Graeme Lee blocked and the goalkeeper recovered to mop up.
On-loan Manchester United teenager Chris Eagles was within inches of a David Beckham-style goal for Wednesday but his 25-yard angled shot on the run curled a fraction wide.
And Elliott blew a 68th minute chance for Hull when he blazed hopelessly wide after Price's impressive cross from the right.
Substitute Adam Proudlock had the chance to claim the winner minutes from the end but glanced his header wide from an inch-perfect cross fired in by Ritchie Partridge.