To avoid the endless accumulation of QTL effects when pyramiding breeding, QTL epistasis plays a role of homeostasis. Four single segment substitution lines with heading date QTLs were applied to construct pyramiding materials of dual QTLs and triple QTLs, so that QTL epistatic effects were allowed to be estimated on heading date in rice. Epistatic components of dual QTL and triple QTL interactions were analyzed via the data from three seasons of two years. Four QTLs can be treated as dominant loci, all appearing superdominance. 75% of dual QTL interactions and 81.25% of triple QTL interactions reached statistically significance, confirming again the prevalence of epistasis. Interactions of four QTLs with three positive effects and one negative effect generated 62.5% negative dual QTL epistatic effects and 57.7% positive triple QTL epistatic effects, forming the balance relationship “positive-negative-positive”. In fact, QTL effects were always neutralized partly by mixed QTL epistatic effects so as to control the infinite accumulation of QTL effects. Specially, the directions of OsMADS50 and Hd3a-2 were always consistent with those of their mixed epistases, suggesting that the QTL or gene could be applied to the pyramiding breeding with different targets. This paper revealed the mechanism of epistatic interactions among four QTLs and provided the gene materials for improving heading date in rice.