Psychological disorders often occur among parents of children with cancer. The current study aimed to explore the longitudinal change of anxiety and depression and their related factors among parents of childhood and adolescence patients with osteosarcoma. A total of 56 childhood and adolescence patients with osteosarcoma who underwent tumor resection and corresponding 104 parents were enrolled. Hospital Anxiety and Depression Scale-Anxiety (HADS-A) and HADS-Depression (HADS-D) of parents were evaluated at baseline (the day of patients’ hospital discharge), 0.5 year, 1 year, 2 years, and 3 years. From baseline to the 3
rd
year, HADS-A (from 8.3 ± 3.1 to 9.4 ± 3.1.
P
< .001), HADS-D score (from 7.7 ± 3.2 to 8.8 ± 2.9,
P
= .001), anxiety rate (from 45.2% to 60.6%,
P
= .038), depression rate (from 38.5% to 57.7%,
P
= .002) were elevated; meanwhile, anxiety severity (
P
= .001) and depression severity (
P
= .001) were also increased. Furthermore, multivariate logistic regression analysis presented that the role of mother, divorced/widowed marital status, declined family annual income, elevated Enneking stage, and amputation were independently correlated with elevated risk of parents’ baseline anxiety or depression (all
P
< .05). Additionally, declined family annual income, elevated Enneking stage, and amputation were independently correlated with increased risk of parents’ 3-year anxiety or depression (all
P
< .05). Anxiety and depression deteriorate with time in parents of childhood and adolescence patients with osteosarcoma, which are affected by parental role, marital status, family annual income, surgery type, and Enneking stage.