"When coaches move into this profession, we know the risks involved and we're prepared for that", said Setien, who may have to do without the injured Luis Suarez for the rest of the season.
Barca spoke to Xavi after their Supercup defeat to Atletico Madrid a week ago, but the midfielder, who is now coaching the Qatari club, Al Sadd, rejected the chance to replace Valverde.
It will be hard without Suarez, he said, but added that he will try to minimize the risks.
"Whether it is fair or unfair, right or wrong, that's not for us to think about".
Quique Setien will take charge of Barcelona for the first time when they host Granada on Sunday night.
Barca refused to settle for one goal as Messi had a shot parried wide by Silva and Griezmann fired into the side-netting from a tight angle.
"We know he went to Barcelona", the Tottenham man told Estadio Deportivo.
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Barcelona will be without the services of star midfielder Frenkie de Jong, who was sent off during a 2-2 derby draw away at Espanyol in its last league fixture.
These were the details of the news The lovely game or bust: New Barcelona manager Quique Setien insists winning ugly is not an option for this day. The goalkeeper has yet to play this year because of a knee ailment. Yesterday the official account of Barcelona shared the video where Setien was seen flaunting his football skills.
He practiced in Setien's first training with the main team on Tuesday and was followed closely by the new coach. Puig also was left out of the list of players selected for the "B" team's game this week, another indication he could join the first team against Granada.
When asked about the prospect of another ex-team-mate, Carles Puyol, taking up a role of sporting director, with Xavi as coach and Gerard Pique as president, Iniesta said: "I truly believe those players, one day, should be at the club, although I don't know in which role".
"I always look at the academy players".
Setien never hid his admiration for Messi, calling him the best player in history, but he doesn't think that will affect the relationship between the coach and the player.