This study applied a steady-state visual evoked potential (SSVEP) based brain–computer interface (BCI) to a patient in lock-in state with amyotrophic lateral sclerosis (ALS) and validated its feasibility for communication. The developed calibration-free and asynchronous spelling system provided a natural and efficient communication experience for the patient, achieving a maximum free-spelling accuracy above 90% and an information transfer rate of over 22.203 bits/min. A set of standard frequency scanning and task spelling data were also acquired to evaluate the patient’s SSVEP response and to facilitate further personalized BCI design. The results demonstrated that the proposed SSVEP-based BCI system was practical and efficient enough to provide daily life communication for ALS patients.