Recent signing Ezra Taylor is included at number 8, while two more newcomers, Cillian Willis and Rob Sweeney, will look to make a big impact from the replacements bench.
Murphy, Cronin, Willis and Keith Matthews have all been passed fit after overcoming knocks, but regular captain John Muldoon (broken arm) and back injury victims Johnny O'Connor and Robbie Morris are notable absentees.
Connacht's most-capped player, Michael Swift, starts in the second row alongside Bernie Upton. This is Swift's eleventh season with the westerners. The 32-year-old scored one of the tries of the season against Leinster last April.
Looking forward to his first competitive match in charge, new Connacht coach Eric Elwood said: "We will go into it with confidence but it is the opening game so neither team has a run of form going into it.
"It's a huge week and I'm feeling a bit of pressure, but it's one of anticipation and everything is geared towards Saturday.
"It's very important we start with a win at home, especially as the next two games are away to the Scarlets and Glasgow Warriors."
He added: "We are missing our talisman, our captain, a very influential player who had stood up to the mark, and got his recognition with his selection for Ireland.
"But we have been talking about developing leaders in the squad, so we are hoping some of the other guys take that mantle on Saturday. We are going to have injuries throughout the season, and we expect people to step up - now is the opportunity.
"We have done a lot of work on unstructured play. We want to move the ball around, we want to play attacking open rugby and create opportunities in attack where both forwards and backs are comfortable with the ball in hand.
"Conversely we have been working on our defence because the game is all about attack in defence and the transition from one to to the other.
"We have got to be ruthless in defence, not leak soft tries, and if people are going to score against us, then they must earn it."
CONNACHT (v Newport Gwent Dragons): Gavin Duffy; Troy Nathan, Niva Ta'auso, Keith Matthews, Fionn Carr; Ian Keatley, Frank Murphy (capt); Brett Wilkinson, Sean Cronin, Jamie Hagan, Michael Swift, Bernie Upton, Michael McCarthy, Ray Ofisa, Ezra Taylor.
Replacements: Adrian Flavin, Ronan Loughney, Rob Sweeney, Dave Nolan, Mike McComish, Cillian Willis, Miah Nikora, Tiernan O'Halloran.