BACKGROUND: Pain sensitivity is critical for preventing non-suicidal self-injury (NSSI) behaviours; however, individuals engaging in such behaviours often exhibit decreased pain sensitivity, which may undermine this natural safeguard. The dorsolateral prefrontal cortex (DLPFC) is a key region involved in pain regulation, and recent approaches using transcranial direct current stimulation (tDCS) to target the DLPFC have shown potential for modulating pain processing and restoring normal pain perception for individuals engaging in NSSI behaviours. AIMS: This study aimed to explore the immediate and short-term effects of a single session of tDCS on pain sensitivity in individuals with NSSI, as well as its secondary effects on mood and NSSI-related factors. METHODS: In this randomised, double-blind, parallel, sham-controlled clinical trial, participants with a history of NSSI were randomly assigned to receive either active or sham tDCS. The intervention consisted of a single 20 min tDCS session targeting the left DLPFC. The primary outcome was pain sensitivity, measured by the pressure pain threshold (PPT) and heat pain score (HPS). Secondary and additional outcomes included NSSI urges, NSSI resistance, self-efficacy in resisting NSSI, mood-related variables and exploratory cognitive-affective processes such as rumination, self-criticism and self-perceived pain sensitivity, assessed at baseline, immediately post-intervention, and at 24 hours, 1 week and 2 weeks follow-ups. RESULTS: For the primary outcomes, no significant differences between groups were observed for pain sensitivity (PPT, p=0.812; HPS, p=0.608). However, an exploratory sensitivity analysis treating each trial as an individual observation revealed a significant effect on HPS (p=0.036). For the secondary and additional outcomes, although there were initial improvements in joyful feelings and reductions in negative affect at 2 weeks post-intervention, these effects did not remain significant after multiple comparison corrections. Notably, reductions in rumination were statistically significant at both 1-week and 2-week follow-ups (1 week, p=0.040; 2 weeks, p=0.042). There were no significant effects on NSSI urges, NSSI resistance, self-efficacy in resisting NSSI or self-criticism. CONCLUSIONS: A single session of tDCS over the left DLPFC did not produce significant changes in pain sensitivity in individuals with NSSI. A sensitivity analysis indicated an effect on heat pain sensitivity, possibly reflecting changes in brain activity, warranting confirmation through neuroimaging. These findings suggest that tDCS warrants further investigation for its potential to influence pain-related cognitive-affective processes in individuals with NSSI.