This study aimed to assess the validity and reliability of the Therapeutic Communication Questionnaire for nurses. This cross-sectional analytical research was conducted in Kashan in 2023. After the translation process, the questionnaire was distributed among the target community. The questionnaire was designed in electronic form (Porsline) and consisted of three sections: demographic information, the Therapeutic Communication Questionnaire for nurses with patients, and a questionnaire on barriers to effective (“nurse–patient”) communication. After completing the questionnaire, the data were entered into SPSS (version 16). Out of 347 participants, 123 (35.47%) were male, with a mean age of 27.07 ± 3.97 years, respectively. The Cronbach's alpha coefficient for the questionnaire was 0.89, and the test–retest reliability (intraclass correlation coefficient, ICC (3,1) was 0.80. The Bartlett's test value was 10368.72, which was statistically significant (P<0.001). The Kaiser-Meyer-Olkin Measure (KMO) index in the results analysis was 0.86. Exploratory factor analysis using principal axis factoring with Promax rotation, combined with scree plot and parallel analysis, supported a three-factor solution explaining 42.46% of the variance. (Only factors 1 and 2 had acceptable reliability.) The questionnaire shows good validity and reliability for Persian speakers. However, cultural differences must be considered, as attitudes influence the nature of communication.