Background Targeted next-generation sequencing is playing an increasingly important role in biological research and clinical diagnosis by allowing researchers to sequence high priority genes at much higher depths and at a fraction of the cost of whole genome or exome sequencing. However, in designing the panel of genes to be sequenced, investigators need to consider the tradeoff between the better sensitivity of a broad panel and the higher specificity of a potentially more relevant panel. Although tools to prioritize candidate disease genes have been developed, the great majority of these require prior knowledge and a set of seed genes as input, which is only possible for diseases with a known genetic etiology. Results To meet the demands of both researchers and clinicians, we have developed a user-friendly website called SoftPanel. This website is intended to serve users by allowing them to input a single disorder or a disorder group and generate a panel of genes predicted to underlie the disorder of interest. Various methods of retrieval including a keyword search, browsing of an arborized list of International Classification of Diseases, 10th revision (ICD-10) codes or using disorder phenotypic similarities can be combined to define a group of disorders and the genes known to be associated with them. Moreover, SoftPanel enables users to expand or refine a gene list by utilizing several biological data resources. In addition to providing users with the facility to create a “hard” panel that contains an exact gene list for targeted sequencing, SoftPanel also enables generation of a “soft” panel of genes, which may be used to further filter a significantly altered set of genes identified through whole genome or whole exome sequencing. The service and data provided by SoftPanel can be accessed at http://www.isb.pku.edu.cn/SoftPanel/. A tutorial page is included for trying out sample data and interpreting results. Conclusion SoftPanel provides a convenient and powerful tool for creating a targeted panel of potential disease genes while supporting different forms of input. SoftPanel may be utilized in both genomics research and personalized medicine. Electronic supplementary material The online version of this article (doi:10.1186/s12859-016-0998-5) contains supplementary material, which is available to authorized users.