Background: Interstitial lung disease (ILD) is a category of chronic lung diseases with more than 200 subtypes. Idiopathic interstitial pneumonia (IIP), Systemic sclerosis (SSc) ILD, and familial interstitial pneumonia (FIP) are three major groups of lung diseases with different causes or with unknown causes. Mucin5B (MUC5B) belongs to the mucin family, which contribute to the lubricating and viscoelastic properties of the whole saliva, normal lung mucus, and cervical mucus. The association between MUC5B rs35705950 and ILDs Risks has been widely studied. However, the results were inconclusive and inconsistent. Methods: In the present meta-analysis, the database PubMed, Embase, Cochrane Central Register of Controlled Trials, CNKI and Chinese Biomedical Literature Database were searched till Aug 20th, 2018. Overall 16 publications with 28 studies, 76345 cases and 18402 controls were included. Results: The results indicated a significant increase of overall IIP risk for TT genotype and T allele of the rs35705950 in all genetic models (TT vs GG, OR=9. 11; TT vs GT+TT, OR=5. 80; GT+TT vs GG, OR=4. 34; T vs G, OR=4. 03. P<0. 0001). Subgroup analysis by subtypes of IIP revealed higher Risks of TT genotype and T allele for IPF and iNSIP (P<0. 05). A significant increase of FIP risk was also found for the TT genotype and T allele of the rs35705950 (TT vs GG, OR=17. 08; GT+TT vs GG, OR=6. 02; T vs G, OR=1. 64. P<0. 05). Conclusion: No significant relations existed between the rs35705950 and SSc-ILD Risks. MUC5B rs35705950 might be a predictor for the susceptibility of IIP and FIP.