Many connective tissue diseases present with various extraarticular manifestations. One of these is interstitial lung disease, which should be a focus of rheumatologists and physical clinicians because of its severe complications. The current study aimed to analyze clinical manifestations of various connective tissue disease-associated interstitial lung disease (CTD-ILDs) patients, evaluating differences in the inflammatory indexes, immunological serologies, and alterations of tumor-associated biomarkers in CTD-ILDs patients. Retrospective analysis of 332 CTD-ILDs patients, enrolled from the ward of the Rheumatology Department in Tongji Hospital, from January 2005 through December 2013, was carried out. The study included idiopathic pulmonary fibrosis (IPF) patients as the positive control group. Gender composition in different CTD-ILDs was statistically different with female predominance, while IPF patients consisted of slightly more males than females. Smoking, exertional dyspnea, and coughing were more common in patients with IPF, while velcro rales were more common in patients with RA-ILD. The percentage of patients with serum AFP, CEA, and NSE levels above upper normal limits was statistically different (more proportion in PM/DM-ILD patients). A positive correlation was found between blood levels of CA125, CA199, CA724, and CYFRA21-1 and patient age in CTD-ILD patients. Differences in gender, age, ILD symptoms, and tumor-associated markers existed not only between CTD-ILDs and IPF patients, but also between different subtypes of CTD-ILD. For early diagnosis of ILD in CTD patients, precise physical examinations are required in patients with subclinical disease. Tumor biomarkers can be screened in ILD patients due to their prognostic potential.