The objective of this study was to perform translation, cross-cultural adaptation, and validation of the SNOT-22 in the Lithuanian language. This is a prospective case-control study. The study was conducted at the University clinic. The sino-nasal outcome test 22 (SNOT-22) was translated into the Lithuanian language; the pilot study involved 34 patients, the test-retest group consisted of 34 patients with chronic rhinosinusitis (CRS), and the control group of 115 patients with no CRS complaints; 36 patients were evaluated before surgery and 3 months after surgery. The results showed a good internal correlation with Cronbach’s alpha-0.89 in the initial test, and 0.93 in the retest; both values suggesting good internal consistency within the SNOT-22. Pearson’s correlation coefficient was 0.72 (p < 0.001), revealing good correlation between the initial scores and the retests scores. Our sample of healthy individuals had a median score of 12 points, and the instrument was capable of differentiating between the healthy and the patient group, demonstrating its validity (p < 0.0001). The statistically significant reduction in the post-operative scores, vis-a-vis pre-operative values, demonstrates the responsiveness of the instrument. The minimally important difference was 13 points in the SNOT-22 score. The Lithuanian version of the SNOT-22 is a valid instrument for assessing patients with CRS. It demonstrated good internal consistency, reproducibility, validity, and responsiveness.