The potential of transcranial direct current stimulation (tDCS) as a non-invasive brain stimulation technique for treating pain has been studied. However, its effectiveness in patients with central post-stroke pain (CPSP) and the impact of lesion location remain unclear. This study investigated tDCS’s pain reduction effects in patients with CPSP. Twenty-two patients with CPSP were randomized into the tDCS or sham groups. The tDCS group received stimulation of the primary motor cortex (M1) for 20 min, five times weekly, for two weeks, and underwent evaluations at baseline, immediately after the intervention, and one week after the intervention. The tDCS group had no significant improvement compared to the sham group in pain, depression, and quality of life. Nevertheless, significant changes were identified within the tDCS group, and the pain trends appeared to be influenced by the lesion location. These findings provide important insights into the use of tDCS in patients with CPSP, which could inform further research and development of pain treatment options.