Abstract: Objective: To explore the relationship of the academic help-seeking, loneliness and professional adaptability, and the mediating role of academic help-seeking between loneliness and professional adaptability in college students of nursing. Methods: Totally 840 college students were assessed with the scale for Academic Help-Seeking behavior, UCLA loneliness Scale and the Professional-Adaptability Scale. Results: The loneliness was negatively associated with professional adaptability (r=-0.269, P<0.01). The dimensions of instrumental help-seeking was negatively associated with loneliness (r=-0.173, P<0.01) and the avoidance help-seeking was positively associated with loneliness (r=0.330, P<0.01); The dimensions of instrumental help-seeking and executive help-seeking was positive associated with professional adaptability (r=0.098-0.299, P<0.01). And the avoidance help-seeking was negatively associated with professional adaptability (r=-0.237, P<0.01). The result of structural equation modeling indicated that instrumental help-seeking and avoidance of academic help-seeking had partial mediation effect between loneliness and professional adaptability, the value of mediating effect was 29.8% and 41.3% respectively. Conclusion: The instrumental help-seeking and avoidance help-seeking play mediating role between loneliness and professional adaptability in college nursing students, indicating that loneliness would reduce professional adaptability by decreasing instrumental help-seeking and improving avoidance help-seeking.