To meet the requirement of lightweight, there are increasing solid shafts being designed to be hollow in transportation industry. In this study, a novel method of flat-knifing cross-wedge rolling (FCWR) with single guide is proposed including a modified roller, a horizontal mill and a single-guide structure, and its key problems are studied by numerical simulations and experimental tests. A mathematical model of FCWR roller is established, which reveals the wedge length of rollers is effectively reduced by modifying knifing wedge from normalized roller. Further, a horizontal multifunctional mill is invented and constructed to carry out the FCWR experiment with single guide. According to the results from the numerical simulations and corresponding experiments, it is observed that the typical defects of hole expansion and knifing groove are absolutely avoided because the improved flat-knifing wedge produces a radial force to shrink the inner hole and avoid the deformation concentration of the outer surface during knifing stage. Moreover, the single guide rolling performed in the horizontal mill efficiently improve rolling stability because the workpiece is restricted into a smaller workspace. To the authors’ knowledge, all these integrated improvements of FCWR roller, single guide rolling and horizontal mill are innovative, which are of great engineering significance to manufacture hollow shafts on account of the advantages of avoiding forming defect, reducing roller diameter, improving rolling stability and simplifying mill structure.