There is a tremendous potential for developing mobile-based productivity tools and occupation specific applications for the semi-literate and illiterate users in India. One-handed thumb use on the touchscreen of smart phone or touch phone is considered as an effective alternative than the use of stylus or index finger, to free the other hand for supporting the occupational activity. In this context, usability research and experimental tests are conducted to understand the role of fine motor control, usability of thumb as the interaction apparatus and the ergonomic needs of users. The paper also touches upon cultural, racial and anthropometric aspects, which need due consideration while designing the mobile interface. Design recommendations are evolved to enhance the effectiveness of one-handed thumb use on smart phone, especially for the benefit of semi-literate and illiterate users.