This work is aimed at enriching a research theme, focused on exploiting the performance in a human–computer numerically controlled (CNC) machine interface (HCMI) environment. A salient contribution of this research effort is focused on adopting the concept of load cell for the system of human-performance measurement. The developed novel system is capable of measuring cognitive and motor action responses simultaneously. The performance measurement system designed for this work may be replicated for other fields where systems are operated through control panels and also where responses of mentally retarded human-beings (or the human beings with the symptoms of Alzheimer disease) are to be observed and evaluated. As regard to the evaluation and trustworthiness of the designed research, search time, motor action time and applied force were selected as response variables to evaluate the CNC machine operator’s performance. Based on Taguchi’s experimental design, a full factorial design consisting of 27 $$(3^{3})$$ experiments was used to collect the data for human performances. The collected data were analyzed using grey relational analysis and analysis of variance (ANOVA) and F-test. ANOVA was carried out using Design-Expert software. The designed research has achieved a reasonable degree of validity through performing confirmation test. This study has presented an effective approach for the optimization of the HCMI environment with multi-performance characteristics based on the combined Taguchi method and Grey relational analysis. Relevance to industry: The findings of this work are directly applicable to the practical field to improve the design of a CNC-machines system. This work suggests that those responsible for the functioning and operation of CNC-machines workstations would have to redesign the system to reduce musculoskeletal injuries and other related problems. The present results can be quite useful for future system designers. It is emphasized that applying ergonomic principles to the design of CNC machines and interfaces can not only help to enhance machine performance and productivity but can also enable the human operator to feel comfortable and secure. As most companies have acquired automated manufacturing technology in recent years to be competitive, ergonomic and safety considerations are of the utmost importance.