This study aims to observe which thumb, the left or right, is used for keystrokes and examine the patterns during two-thumb key entry on a smartphone QWERTY soft keyboard. A total of 36 college students, including 18 left-handed and 18 right-handed, were recruited for testing, and they had 9.7 years of smartphone use experience on average. A smartphone application was implemented, and whether the left or right thumb was used for touch interactions was recorded for each of the 26 letter keys. As a result, it was found that there were slightly more letter keys that were statistically more often tapped by the left thumb during the two-thumb key entry on the QWERTY soft keyboard, regardless of the participant’s handedness. In addition, all the letter keys were touched statistically more often with the relatively closer one of both thumbs, except for the letter keys G and V in the center. It seemed that the distance between keys and thumbs was regarded as the most important factor influencing the thumb choice for keystrokes, followed by the habituated experience of using physical QWERTY keyboards.