McDermott has been installed as successor to Tony Rea at the Twickenham Stoop after quitting his post as assistant coach at Leeds.
The former Great Britain prop enjoyed a dream start as Quins powered 8-0 ahead after 11 minutes but Saints quickly assumed command with three converted tries to lead 18-8 at the break.
McDermott�s men, led by the inspirational Mark McLinden, continued to battle gallantly after the restart and could ultimately consider themselves unfortunate to depart Merseyside pointless.
The Londoners received the perfect early boost as they opened the scoring from the first set of six when prop Daniel Heckenberg lunged over with barely 90 seconds played.
Henry Paul landed the goal and the Londoners launched a succession of swift attacks which threatened to penetrate the hosts once again.
Three handling errors from St Helens inside the first 10 minutes characterised their nervy start, and Quins soon extended their advantage moments later when Paul landed a penalty following Paul Anderson�s high shot on Zebastian Luisi.
However, two minutes later a mistake in the visitors� rearguard allowed youngster Matty Smith to touch down under the posts for his first try in St Helens colours.
Teenage half-back Smith, making only his second senior start for Saints with Sean Long nursing a leg injury, turned to rugby league despite being a promising footballer with Everton.
Smith�s influence began to grow and his clever kick into the right corner narrowly evaded Ade Gardner before another kick rebounded off a post as Harlequins breathed a sigh of relief in the face of mounting pressure.
They were finally undone after 27 minutes when Keiron Cunningham scampered over in trademark fashion from acting half, with Jamie Lyon again converting to edge Saints 12-8 ahead.
When Harlequins full-back McLinden was sinbinned on the half hour mark for holding down, Saints swiftly capitalised when the ball passed through five pairs of hands in a bewildering move which Nick Fozzard finished off from close range.
Lyon again converted to put St Helens firmly in command at 18-8 at the break but the response from the visitors was immediate as Tyrone Smith shrugged off Paul Wellens to cross in the left corner.
Shortly before the hour mark, Nick Bradley-Qalilawa crashed over in the right corner but Paul failed to convert to leave the scores finely poised at 24-18.
The pendulum swung back towards St Helens when the mercurial Lyon ushered Gardner over into the right corner, and although Lyon failed to convert, the Australian centre soon added a penalty to send Saints 30-18 ahead.
Yet again, though, the visitors hit back when McLinden glided over for a delightful effort which Paul converted, but it was not enough to save McDermott from a losing start to his Harlequins tenure.
St Helens: Wellens, Gardner, Lyon, Gilmour, V. Anderson, Pryce, Smith, Cayless, Cunningham, P. Anderson, Wilkin, Graham, Hooper. Replacements: Roby, Fozzard, Hardman, Fa'asavalu.
Harlequins RL: McLinden, Smith, Gafa, Lucky Luisi, Bradley-Qalilawa, Dorn, Leuluai, Mills, Randall, Heckenberg, Purdham, Hopkins, Paul. Replacements: Budworth, Weisner, Mbu, Tookey.
St Helens: (18) 30. Tries: Smith, Cunningham, Fozzard, Graham, Gardner. Goals: Lyon 5.
Harlequins RL: (8) 24. Tries: Heckenberg, Smith, Bradley-Qalilawa, McLinden. Goals: Paul 4.
Referee: P Bentham (Warrington)