Objective To investigate the current status of personal mastery and its influencing factors for mothers of hospitalized neonates in the Neonatal Intensive Care Unit (NICU). Methods A total of 390 mothers of hospitalized neonates in NICU were selected. The general data inventory, Personal Mastery Scale (PMS), Breastfeeding Self⁃Efficacy Scale⁃Short Form, Perceived Social Support Scale, Self⁃Rating Anxiety Scale, Edinburgh Postnatal Depression Scale were used to perform questionnaire investigation on mothers of hospitalized neonates in NICU. PMS score were compared between mothers of neonates with different demographic characteristics. The correlation of PMS score in neonates' mothers with Breastfeeding Self⁃Efficacy Scale⁃Short Form, Perceived Social Support Scale, Self⁃Rating Anxiety Scale, Edinburgh Postnatal Depression Scale was analyzed. The influencing factors for personal mastery of neonates' mothers were analyzed by employing the multiple linear regression model. Results The total score of PMS of mothers of hospitalized neonates in NICU was 26.37±4.63. There was a statistically significant difference in PMS score between mothers of hospitalized neonates in NICU with different occupations, residences, monthly household income, medical insurance type, gestational age of neonates, and birth weight of neonates (P<0.05). The results of correlation analysis revealed that PMS score of mothers of hospitalized neonates in NICU negatively correlated with Self⁃Rating Anxiety Scale and Edinburgh Postnatal Depression Scale, whereas positively correlated with Breastfeeding Self⁃Efficacy Scale⁃Short Form and Perceived Social Support Scale (P<0.05). The results of multiple linear regression analysis interpreted that breastfeeding self⁃efficacy, perceived social support, anxiety, postpartum depression were the influencing factors for personal mastery of mothers of hospitalized neonates in NICU (P<0.05). Conclusion Personal mastery of mothers of hospitalized neonates in NICU is at the medium level, breastfeeding self⁃efficacy, perceived social support, anxiety, and postpartum depression may affect personal mastery in neonates' mothers.