This study aimed to clarify the relationships among developmental characteristics of retinoblastoma (RB) infants, mother-infant interaction, and mental health of mothers. Prospective studies were conducted twice with 13 dyads of mothers and infants who were between one (Time 1) and two years old (Time 2). Cross-sectional and longitudinal analyses were performed. The mean Developmental Quotients (DQ) significantly decreased between Time 1 and Time 2 (p < .05). Four (30.8%) infants showed DQ p < 85 at Time 1. They showed a DQ below the borderline at Time 2 and their developmental changes were different from RB infants in the normal DQ range. Infant Behavior Checklist-R (IBC-R) scores negatively correlated with DQ (p < .05). The mothers’ Japanese Nursing Child Assessment Teaching Scale (JNCATS) scores were significantly higher than the normative mean. The IBC-R scores negatively correlated with mothers’ JNCATS scores at Time 1 (ρ = -.66, p < .05) and positively correlated with the child domain scores on the Parenting Stress Index at Time 2 (ρ = .62, p < .05). Some RB infants showed a developmental delay. Mother-child interactions were negatively affected and mothers recognized their infants’ problem. The support needs to be provided in early infancy.