Background: In China, patients with somatoform disorders (SFD) often seek medical treatment repeatedly in outpatient clinics of general hospitals, which increases unreasonable medical expenses. It is imperative to provide early screening to these patients and specialized treatment to reduce the unnecessary cost. This study aimed to screen patients with SFD in general hospitals using a new Chinese questionnaire and explore the characteristics and economic burden of these patients. Methods: Patients (n = 1497) from the outpatient department of neurology, cardiology and gastroenterology of three large general hospitals were included. Participants were screened using a newly developed questionnaire, the Self-screening Questionnaire for Somatic Symptoms (SQSS), to identify the patients with SFD (total SQSS score ≥ 29 points). We compared the demographics and clinical information of patients with and without SFD. Logistic regression was used to explore potential factors related to medical expenses, visits to doctors and sick leave days taken. Results: The frequency of detection of patients with SFD was 17.03%. There were significant differences in employment, doctor visits, symptom duration, medical expenses, sick leave days, PHQ-15 scores, and PHQ-9 scores between patients with SFD and without SFD. General nonspecific somatic symptoms were frequently present in patients with SFD. Several potential factors were associated with higher medical expenses, repeated doctor visits, and sick leave days taken in the regression analysis. Conclusion: The findings indicate that patients with SFD are common in general hospitals, and their direct and indirect economic burden is higher than that of non-SFD patients, which indicates that more screening effort should be made to this group to early identify their problems. Certain characteristics were identified among patients with SFD and several factors were associated with negative consequences of SFD, all of which might be prevented by developing a preventive intervention program to reduce the economic burden of the patients.