Background Happiness and professional autonomy in nurses increase job satisfaction, reduce turnover and improve the quality of healthcare services. Aims The present study aimed to examine the correlation between happiness and professional autonomy in Iranian nurses. Methods This descriptive-correlational study was conducted on 371 nurses in 2017. The participants were selected via two-step random sampling. Data were collected using the Oxford Happiness Inventory and Dempster Practice Behaviors Scale within the score ranges of 0–87 and 30–150, respectively. Data analysis was performed in SPSS version 16. Results Mean score of happiness among nurses was 43.1 ± 13.3 and the mean score of professional autonomy was 96.4 ± 13.5. According to Pearson's correlation coefficient, professional autonomy had a positive, significant correlation with happiness ( r = 0.481; p < 0.001). In addition, the results of regression analysis indicated that professional autonomy could predict 23% of the happiness variance in the nurses ( p < 0.001). Conclusions According to the results, the level of happiness in Iranian nurses was favourable, whereas the level of professional autonomy was moderate. Considering the significant correlation between happiness and professional autonomy, attention should be paid to the simultaneous enhancement of these variables to improve the efficiency of nursing care.