Kay Kay Menon was the first choice for the lead role (K), but he declined suggesting Kashyap to cast an actor having stardom. Anurag then offered SRK the role, who ultimately declined as he felt that the movie promotes 'anti-smoking' feelings. John Abraham was the only star-actor to love the script, and agree to do it.
John Abraham who quit smoking, had to smoke 99 cigarettes a day to get into the character which resulted in his lungs getting affected.
Anurag Kashyap stated "Show me another actor other than Aamir Khan who can refuse two big proposals of doing a Yashraj film and a Mani Ratnam film (incidentally, I worked on both these films that he rejected) and choose absolutely risky Kabul Express or No Smoking... SRK didn't have the courage. Hrithik Roshan, the other day asked me at a friend's party, in front of Kunal Kapoor as witness, 'Why didn't you come to me with No Smoking? I heard the concept somewhere and liked it." He couldn't remember who told him and where, and I did not remind him that it was me who narrated him the concept but at that time he wanted to do something like Starsky and Hutch. Problem is no actor barring Aamir and John have the intelligence or imagination to see a film before it's made."
Anurag Kashyap's then-assistant Vikramaditya Motwane (later director of Udaan) appears in a shot where he shows us the middle finger, smoking a cigar in John Abraham's office right after John passes an order to ban the smoking in his office. The resignation letter is shown to be written by Vikramaditya Motwane.