Childhood maltreatment and genes underlie vulnerability to suicidal behaviours (SB), possibly by affecting the constitution of endophenotypes such as anger traits. The CREB protein has been implicated in antidepressant response, suicide and mood disorders in general. The aim of this study was to investigate if CREB1 gene is associated with SB and/or anger-related traits and if these associations are modulated by childhood maltreatment. Five hundred and thirty-four male suicide attempters and 357 male non-suicide attempters were genotyped for several polymorphisms within CREB1 gene. Four hundred and thirty-seven (156 non-suicide attempters and 281 suicide attempters) completed the State-Trait Anger Expression Inventory (STAXI) and 288 (265 suicide attempters and 23 controls) fulfilled the Childhood Trauma Questionnaire (CTQ). In total, 72 males had experienced childhood sexual abuse. Our results did not show any significant association between CREB1 and suicide behaviour. We found a significant interaction showing that CREB1 rs4675690 polymorphism modulated the effect of childhood sexual abuse on adulthood anger-out levels (P = 0.003). Sexually abused subjects carrying the CC genotype showed higher anger-out scores than T allele carriers, whereas no difference was observed in non-sexually abused subjects. CREB1 rs4675690 polymorphism modulates the association between childhood sexual abuse and adulthood anger-trait level. This is, to our knowledge, the first study to show such an interaction and to highlight the main effect of this gene on modulating the effect of child abuse on psychopathologies and warrant further investigation on this topic.