Cancellation tasks have been widely used to neurologically assess selective attention and visual search in various clinical and research settings. However, there is still a lack of evidence regarding the effect of the level of task difficulty on brain activity in the prefrontal cortex (PFC). This study implemented cancellation tasks to investigate the effects of varying task difficulty on oxygenated hemoglobin (oxy-Hb) concentrations. Data from 21 healthy adults were analyzed based on performance during three-block-design types of cancellation tasks with different T/D ratios (i.e., 1/9, 2/8, and 3/7). Performance was assessed via the number of correct responses, incorrect responses, hit ratios, achievement ratios, and performance scores (PS), while PFC activity was examined using near-infrared spectroscopy. Both the numbers of correct responses and PS were the lowest for the smallest T/D ratio. Similarly, we observed that the oxy-Hb concentration in the PFC was significantly increased during the task. Our results support the findings of previous studies that used conventional cancellation tasks, thus suggesting that block design types are suitable for examinations in the same contexts. Regarding the above-mentioned changes in the oxy-Hb concentration, the findings suggest that the PFC region is involved in selective attention.