The success of RNA interference (RNAi) depends on the interaction between short interference RNAs (siRNAs) and mRNAs. Design of highly efficient and specific siRNAs has become a challenging issue in applications of RNAi. Here, we present a detailed survey on the state-of-the-art siRNAs design, focusing on several key issues with the current in silico RNAi studies, including: (i) inconsistencies among the proposed guidelines for siRNAs design and the incomplete list of siRNAs features, (ii) improper integration of the heterogeneous cross-platform siRNAs data, (iii) inadequate consideration of the binding specificity of the target mRNAs and (iv) reduction in the off-target effect in siRNAs design. With these considerations, the popular in silico siRNAs design rules are reexamined and several inconsistent viewpoints toward siRNAs feature identifications are clarified. In addition, novel computational models for siRNAs design using state-of-art machine learning techniques are discussed, which focus on heterogeneous data integration, joint feature selection and customized siRNAs screening toward highly specific targets. We believe that addressing such issues in siRNA study will provide new clues for further improved design of more efficient and specific siRNAs in RNAi. 