Nuclear receptors are a superfamily of transcription factors including the steroid hormone receptors, non-steroid hormone receptors and the orphan nuclear receptor family. Retinoic acid-related orphan receptor (ROR)β, as a member of the orphan nuclear receptor family, plays an important regulatory role in the maintenance of a variety of physiological and pathological processes. RORβ has been determined to act as an osteogenic repressor in regulating bone formation, and is involved in regulating circadian rhythm. The findings of recent studies concerning the association between tumorigenesis and circadian rhythm have shown that an aberrant circadian rhythm may promote tumorigenesis and tumor progression. The mechanisms discussed in this review demonstrate how aberrant RORβ-induced circadian rhythm may become a new direction for future studies on tumorigenesis and strategy design for cancer prevention.