Background The aim of this study was to investigate the expression of MUC5AC and MUC5B messenger RNAs (mRNAs) and localization of these proteins in human sinus mucosa of chronic rhinosinusitis (CRS) and CRS with nasal polyposis (CRS/NP). Methods Maxillary sinus ostia mucosa was harvested from patients undergoing endoscopic sinus surgery for CRS, CRS/NP, and non-CRS pathologies (control). Then, sinus mucosa was analyzed using reverse-transcription polymerase chain reaction to detect mRNA of MUC5AC and MUC5B. Hematoxylin and eosin staining and immunofluorescent staining were used to localize MUC5AC and MUC5B proteins in the sinus mucosa. Results mRNAs of MUC5AC and MUC5B in the sinus mucosa of CRS and CRS/NP were significantly increased compared with that in normal sinus mucosa (p < 0.01), and no significant difference was found between the mucosa of CRS and that of CRS/NP (p > 0.05). MUC5AC protein was expressed mainly in the goblet cells, and MUC5B expression was located in the submucosal glands cells and the epithelia of sinus mucosa. ARPC in staining of MUC5AC and MUC5B were found no different between the CRS group and the CRS/NP group (p > 0.05), whereas they were significantly lower in the normal group compared with the other two groups, respectively (p < 0.05). Conclusion This study showed that MUC5AC and MUC5B mucin genes were up-regulated in sinus mucosa of CRS and CRS/NP. MUC5AC and MUC5B may play an important role in the pathogenesis of CRS and NP.