Several circulating miRNAs identified in the plasma of smokers have been implicated as promoters of nasopharyngeal and lung carcinoma. To investigate the plasma profile of miRNAs in subjects who reduces the number of smoked cigarettes and who quit after six months. We accompanied 28 individuals enrolled in a Smoking Cessation Program over 6 months. At Baseline, clinical characteristics, co-morbidities, and smoking history were similar among subjects. After 6 months, two groups were defined: who successfully quitted smoking (named "quitters", n = 18, mean age 57 years, 11 male) and who reduced the number of cigarettes smoked (20-90%) but failed to quit smoking (named "smokers", n = 10, mean age 52 years, 3 male). No significant clinical changes were observed between groups at baseline and after a 6-month period, however, quitters showed significant downregulations in seven miRNAs at baseline: miR-17 (- 2.90-fold, p = 0.029), miR-20a (- 3.80-fold, p = 0.021); miR-20b (- 4.71-fold, p = 0.027); miR-30a (- 3.95-fold, p = 0.024); miR-93 (- 3.63-fold, p = 0.022); miR-125a (- 1.70-fold, p = 0.038); and miR-195 (- 5.37-fold, p = 0.002), and after a 6-month period in 6 miRNAs: miR-17 (- 5.30-fold, p = 0.012), miR-20a (- 2.04-fold, p = 0.017), miR-20b (- 5.44-fold, p = 0.017), miR-93 (- 4.00-fold, p = 0.041), miR-101 (- 4.82-fold, p = 0.047) and miR-125b (- 3.65-fold, p = 0.025). Using time comparisons, only quitters had significant downregulation in miR-301b (- 2.29-fold, p = 0.038) after 6-month. Reductions in the number of smoked cigarettes was insufficient to change the plasma profile of miRNA after 6 months. Only quitting smoking (100% reduction) significantly downregulated miR-301b related to hypoxic conditions, promotion of cell proliferation, decreases in apoptosis, cancer development, and progression as increases in radiotherapy and chemotherapy resistance.