Objective To compare the effects of smoking and non smoking on postoperative pain of laparoscopic cholecystectomy. Methods Sixty patients having underwent selective laparoscopic cholecystectom were divided into smoking group and non smoking group by random digits table with 30 cases each. In smoking group, 14 cases quitted smoking within 1 week before operation. The Fagerstrom test of nicotine dependence (FTND) was evaluated before operation in smoking group, and FTND ≥ 6 scores was in 11 cases. The visual analog score (VAS), Bruggrmarm comfort score (BCS), sedation-agitation score (SAS), immediately, 15 min, and 30 min after entering postanesthesia care unit (PACU) and leaving PACU was evaluated. The operation time, anesthesia time, wake up time, extubation time, PACU time, using rate of remedial measures and untoward reaction were recorded. Results There were no statistical differences in operation time, anesthesia time, wake up time, extubation time, SAS and incidence of untoward reaction between 2 groups (P>0.05). The PACU time and using rate of remedial measures in smoking group were significantly higher than those in non smoking group:(39.7 ± 5.1) min vs. (31.3 ± 6.1) min and 30.0% (9/30) vs. 0, and there were statistical differences (P<0.05). The VAS immediately, 15 min and 30 min after entering PACU and leaving PACU in smoking group was significantly higher than that in non smoking group: (2.90 ± 0.85) scores vs. (1.00 ± 0.83) scores, (2.70 ± 0.47) scores vs. (0.73 ± 0.69) scores, (2.60 ± 0.56) scores vs. (1.13 ± 0.73) scores, (2.23 ± 0.57) scores vs. (1.13 ± 0.73) scores; and the BCS was significantly lower than that in non smoking group:(1.80 ± 0.61) scores vs. (2.90 ± 0.99) scores, (1.90 ± 0.31) scores vs. (2.87 ± 1.00) scores, (2.10 ± 0.31) scores vs. (2.47 ± 0.82) scores, (2.17 ± 0.38) scores vs. (2.47 ± 0.82) scores, and there were statistical differences (P<0.05). The VAS immediately after entering PACU in patients of FTND ≥ 6 scores was significantly higher than that in patients of FTND<6 scores:(3.6 ± 0.7) scores vs. (2.5 ± 0.7) scores, the BCS was significantly lower than that in patients of FTND <6 scores:(1.5 ± 0.5) scores vs. (2.0 ± 0.6) scores, and there were statistical differences (P<0.05). The VAS immediately after entering PACU in patients of non- quit smoking was significantly higher than that in patients of quit smoking: (3.4 ± 0.7) scores vs. (2.4 ± 0.6) scores, and there were statistical differences (P<0.05). Conclusions Smokers have more severe postoperative pain in laparoscopic cholecystectomy and higher postoperative opioid requirement than nonsmokers. Quit smoking before surgery will reduce postoperative pain and related complications. Appropriate increase of analgesic drugs can prevent postoperative pain in patients with smoking.